Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

Users Online : 156731

AbstractMaterial and MethodsResultsDiscussionConclusionReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : February | Volume : 17 | Issue : 2 | Page : EC40 - EC45 Full Version

Profile of HER2/neu Expression in Surface Epithelial Ovarian Tumours: A Clinicomorphological Study


Published: February 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/61283.17547
Abbirami Rajarajan, Kalaivani Amitkumar, Muthu Sudalaimuthu

1. Postgraduate, Department of Pathology, SRM Medical College Hospital and Research Centre, Chengalpattu, Tamil Nadu, India. 2. Professor, Department of Pathology, SRM Medical College Hospital and Research Centre, Chengalpattu, Tamil Nadu, India. 3. Professor, Department of Pathology, SRM Medical College Hospital and Research Centre, Chengalpattu, Tamil Nadu, India.

Correspondence Address :
Dr. Kalaivani Amitkumar,
S1, Thanya Regency, 11/61 Ganesh Nagar Main Road, Selaiyur, East Tambaram, Chennai, Tamil Nadu, India.
E-mail: abbidoc1@gmail.com

Abstract

Introduction: Surface Epithelial Ovarian Tumours (SEOT) are most prevalent tumours and account for about two third of all ovarian cancers. Survival of ovarian carcinoma is poor despite optimal surgical and chemotherapeutic management. Evaluation of new diagnostic and prognostic Immunohistochemical (IHC) markers will be essential in this aspect.

Aim: To evaluate quantitatively the profile of Human Epidermal growth factor Receptor 2 (HER2)/neu IHC expression with standard scoring system in SEOTs and their association with various clinicpathologic variables (age, laterality, CA 125 levels, histological subtype and FIGO staging).

Materials and Methods: The present ambispective study was done in the Department of Pathology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu, India, from August 2020 to August 2022 with a sample size of 166 cases. All the histopathological samples of SEOT during the study period from August 2020 to August 2022 (prospective) and all borderline, malignant and few benign cases from June 2016 to August 2020 (retrospective) were also included in the study. Cases for which slides and blocks were not available and patient treated with neoadjuvant chemotherapy or radiotherapy were excluded in the study. For prospective cases after getting clinical history and Cancer Antigen 125 (CA 125) level, specimens were fixed, processed and Haematoxylin and Eosin (H&E), IHC staining was done as per standard lab protocol, for retrospective cases clinical history, CA 125 levels, pathological diagnosis and tissue blocks were retrieved, IHC performed and finally both prospective and retrospective cases HER2/neu IHC expression association was studied related to clinicopathological parameters.

Results: Out of total sample, SEOT was the most common (n=184, 76.98%) tumour cases, followed by germ cell tumours (n=42, 17.57%) cases and least common was sex cord stromal tumour (n=13, 5.43%). HER2/neu had higher IHC expression in malignant tumours and showed statistically significant positive association with age (p-value=0.001), CA 125 level (p-value-0.001), and histological diagnosis (p-value <0.001), but there is no significant association with size of tumour (p-value=0.786), parity (p-value=0.717), laterality (p-value=0.514) and the International Federation of Gynaecology and Obstetrics (FIGO) grading (p-value=0.274).

Conclusion: Malignant tumours had high HER2/neu IHC expression, thus emphasising its carcinogenic role and helps in the diagnostic differentiation of benign and borderline tumours with malignant potential from actual malignant tumours and can be a therapeutic target in future.

Keywords

Cancer antigen 125, Human epidermal growth factor receptor 2, Immunohistochemical

Ovarian cancer is the seventh most common cancer to cause death worldwide (1). In India, ovarian tumour ranks third in female genital malignancy, World Health Organisation (WHO) 2020 classified ovarian cancer based on histomorphological features and origin of cell (2). Surface Epithelial Ovarian Tumours (SEOT) are most prevalent tumours and accounts about two-third of all ovarian cancers (3). SEOT show high proliferative activity and more than 80% of SEOT patients have increased serum Cancer Antigen 125 (CA 125) values at the time of diagnosis and on serial screening of CA 125 level which is correlating with disease status in most of the cases (4),(5). Despite advances in surgical procedures and chemotherapeutic drugs, chemotherapy related morbidity and mortality is still prevalent. Hence, appropriate diagnosis as benign, borderline and malignant tumours along with histological typing is important for selecting patients with a favourable or worse clinical outcome, it also helps for improving the individualised treatment planning of patients (6). Evaluation of new diagnostic and prognostic markers will be essential in this aspect.

Human Epidermal growth factor Receptor 2 (HER2)/neu (c-erbB2) is a proto-oncogene and is mainly expressed in epithelial tissue and activated due to its amplification (7). HER2/neu overexpressed in 15-30% of invasive breast cancers, and could be a possible therapeutic target in epithelial ovarian cancer too (8). Nearly 20-30% patients with ovarian carcinoma will have HER2/neu overexpression. Berchuck et al., were the first to establish that overexpression of HER2 gene will have poor survival rate in high stages of epithelial surface ovarian cancer (9).

In India, currently only little reported details about expression of HER2/neu in ovarian cancer is available (9),(10),(11),(12). Hence, this study is done to identify the diagnostic and prognostic role of HER2/neu Immunohistochemical (IHC) marker. The aim of the present study was to evaluate the immunological expression of HER2/neu in SEOT and to compare HER2/neu values with clinicopathological parameters {age, laterality, CA 125 levels, histological subtype and The International Federation of Gynaecology and Obstetrics (FIGO) staging}.

Material and Methods

The present ambispective study was conducted in the Department of Pathology, SRM Medical College Hospital and Research Centre, Kattankulathur, Chengalpattu, Tamil Nadu, India, from August 2020 to August 2022 with a sample size of 166 cases. Ethical clearance was obtained from Institutional Ethical Committee (IEC NO:2418).

Inclusion criteria: Retrospective cases with borderline, malignant diagnosis and few of benign cases from June 2016 to August 2019 were included in the study.

Exclusion criteria: Cases for which slides and blocks were not available, blocks with insufficient tissue material for IHC and patients treated with neoadjuvant chemotherapy or radiotherapy were excluded from the study.

Study Procedure

All histopathological samples of SEOT cases received between August 2020 and August 2022 were studied. Analysis of all cases (both prospective and retrospective) was done between August 2020 to August 2022. Study included 166 cases of SEOT. Clinical details of the patient, morphological findings were recorded. CA 125 levels were available for 140 cases. For retrospective cases, tissue blocks and Haematoxylin and Eosin (H&E) stained slides were collected. In prospective cases, specimens were fixed, processed and H&E staining was done as per standard lab protocol. Tumours were classified according to WHO classification of SEOTs 2020 (13). HER2/neu, rabbit monoclonal antibody (clone:EP3) IHC staining was performed in all benign, borderline and malignant SEOT as per the standard protocol followed in the present study histopathology lab and associated with clinicopathological parameters (age, laterality, CA 125 levels, histological subtype and FIGO staging (13)). CA 125 level <35 U/mL considered to be normal (14). Scoring for HER2/neu was done as per the (Table/Fig 1) (15).

Statistical Analysis

All data were analysed using Statistical Package for the Social Sciences (SPSS) software version 21.0. Numerical values like age were represented in mean and standard deviation. For test of significance, Chi-square test was used. Association between HER2/neu IHC expression and clinicopathological parameters were tested by Student’s t-test for two categories and Analysis of Variance (ANOVA) test for more than two categories. The p-values <0.05 were considered statistically significant.

Results

Distribution of ovarian tumours: A total of 239 cases of ovarian tumours received between the period of 2016 June to 2022 June. Out of which SEOT was the most common tumours occurring as 184 (76.98%) cases, followed by germ cell tumours of 42 (17.57%) cases and least was sex cord stromal tumours of 13 (5.43%) cases. Eighteen cases were not included in the study as per exclusion criteria and finally 166 cases were included in the study.

Distribution of cases according to age group: On analysing the distribution of age among the subjects, the most common age group was found between 41-50 years of age seen in 50 (30.12%) cases and least were less than 20 years of age group seen in 4 (2.41%) cases (Table/Fig 2).

Distribution based on laterality of SEOT: On evaluation of all cases of SEOT, unilateral right ovarian involvement was more common and seen in 78 (46.99%) cases followed by 73 (43.98%) cases of unilateral right ovarian involvement and least 15 (9.04%) cases had bilateral ovarian involvement.

Gross features: On gross examination of all cases, predominantly 96 (57.83%) cases had cystic lesion followed by 24 (14.46%) cases who had cystic lesion along with solid areas and least is 2 (1.20%) cases with predominantly solid lesion. The gross features of few cases of SEOTs are shown in (Table/Fig 3)a,b.

Histological type: On evaluating the total cases, most common histological type among SEOTs were of serous type seen in 84 (50.6%) cases followed by mucinous type noted in 61 (36.75%) cases, seromucinous type noted in 14 (8.43%) cases, least were 4 (2.41%) cases of endometrioid type and 3 (1.8%) cases of transitional type.

Histopathological diagnosis: On analysing the histopathological diagnosis, out of 166 cases, predominantly 132 (79.52%) cases were found to have benign tumours followed by 22 (13.25%) cases of malignant SEOTs and least is 12 (7.23%) cases of borderline tumour.

Evaluation of CA 125 level with histopathological diagnosis: On evaluating the mean serum CA 125 level with histopathological diagnosis, high serum CA 125 Level was noted among Malignant tumours with a mean of 693.19 U/mL and least in benign tumours with a mean CA 125 level of 31.87 U/mL and their association was statistically significant (p-value <0.05) (Table/Fig 4).

Comparison of serum CA 125 level with histological type: Comparing the serum CA 125 level with histological type distribution, Endometroid type had higher mean of CA 125 level with 660.13 U/mL and least in seromucinous type with 25.65 U/mL and their association is statistically significant (p-value <0.05) (Table/Fig 5).

Distribution of benign tumours: On analysing the total cases, the most common histological type of benign tumours were 61 (36.74%) cases of serous cystadenoma and least is 1 (0.6%) case of transitional histological types (Table/Fig 6).

Distribution of borderline tumours: On evaluation of borderline SEOTs, the most common histological type were 6 (50%) cases of mucinous borderline tumour followed by 4 (33.33%) cases of serous borderline tumour and least were 2 (16.7%) cases of seromucinous borderline tumours.

Distribution of malignant tumours: On analysis of malignant SEOTs, the most common histological subtype were 9 (40.9%) cases of serous cystadenocarcinoma followed by 6 (27.28%) cases of mucinous cystadenocarcinoma and least was 4 (18.14%) cases of endometrioid carcinoma (Table/Fig 7).

FIGO staging for malignant tumours: On evaluating the FIGO staging in 22 malignant cases, predominantly 7 (4.22%) cases had IA stage followed by 5 (3.01%) cases with IC stage, 2 (1.20%) cases had IIB and IIIC (1.20%) stage (Table/Fig 8).

Distribution of pathological tumour stage: On analysing the pathological tumour stage among 22 malignant cases, predominantly 7 (4.22%) cases had pT1a followed by 4 (2.41%) cases with pT1c stage (Table/Fig 9).

Frequency of nodal involvement in malignant SEOTs: Out of 22 malignant cases among the subjects, only 1 (4%) case had nodal involvement N1b and 18 (82%) cases had no nodal involvement (N0) followed by 3 (14%) cases in which the nodal involvement could not be assessed (Nx).

Distribution of metastasis in malignant SEOTs: On analysis of metastatic status of 22 malignant SEOTs, in 19 (11.45%) cases the metastatic status could not be assessed (Mx) and in 3 (1.81%) cases there was no evidence of metastasis (M0).

Distribution of HER2/neu grades among study population: On evaluating the total 166 cases predominantly 146 (87.95%) cases had 0 HER2/neu grading followed by 14 (8.43%) cases had 1+HER2/neu grading, both showed HER 2/neu negative expression. HER2/neu positive expression of 2+ grading of 3 (1.81%) cases and 3+ grading of 3 (1.81%) cases were noted. HER2/neu showed membranous positivity and the IHC expression of HER2/neu showed in (Table/Fig 10)a-c.

Association of age group with the HER2/neu grading: Comparing the age group with HER2/neu grading distribution, 41-50 years had higher proportion of 0 grading with 30.82%, 21-30 years had higher proportion of 1+ grading with 35.71%, and ≤20 years had higher proportion of 2+ grading with 33.33%. The association between them are statistically significant (p-value <0.05) (Table/Fig 11).

Association of CA 125 level with HER2/neu grading: Comparing the CA 125 level with HER2/neu grading distribution, 2+ grading had higher mean of CA 125 level with 472.19 followed by 3+ grading with 327.12 and least in 0 grading with 96.52 and the association between them are statistically significant.

Association of HER 2/neu grading with the histopathological diagnosis: Comparing the histopathological diagnosis with HER2/neu positivity distribution, malignant had higher proportion of HER2/neu positivity with 18.18% followed by borderline with 16.66% and least in benign with 0% and the association between them are statistically significant (p-value <0.05). Evaluation of HER2/neu IHC expression among malignant SEOTs: Among 22 malignant tumours, 4 (18%) cases showed positive expression with HER2/neu IHC expression while 18 cases (82%) showed negative expression
(Table/Fig 12).

Association of histopathological type with HER2/neu positivity: Comparing the histological type with HER2/neu positivity distribution, mucinous had higher proportion of HER2/neu positivity with 4.91% followed by serous with 3.57% and least in seromucinous with 0%. The association between them is not statistically significant (p-value >0.05).

Association of FIGO staging with IHC markers in malignant SEOTs: Comparing the FIGO stage with HER2/neu positivity distribution in 22 malignant cases, stage II had higher proportion of HER2/neu positivity with 50% followed by stage I with 14.28% and least in stage III with 0% and the association between them is not statistically significant (p-value >0.05) (Table/Fig 12).

Association of size, laterality and parity of tumours with HER2/neu IHC expression: On comparing the parity, laterality, size of tumours with HER2/neu IHC expression there was no significant association with p-values 0.717, 0.514 and 0.786, respectively.

Discussion

On comparing with other ovarian tumours SEOTs have high likelihood of changing into malignant ovarian tumours and therefore prompt diagnosis and timely intervention is important for successful patient treatment and management. Hence, the current study was done with a motive to identify the individuality of IHC marker to assist in the proper subtyping and grading of SEOT.

Frequency of SEOT in the study population: In the present study, 184 cases out of 239 were SEOTs, followed by 42 cases of germ cell tumours and 13 cases were sex cord stromal tumours. Hence, this study clearly states that SEOT is the most common (76.98%) ovarian tumours. Similar results were obtained by Buchynska LG et al., at National Institute of Cancer at Uttar Pradesh, and Mondal SK et al., at Kolkata, India (16),(17).

Age of occurrence: It can be detected that benign SEOT tumours presented more in younger females while malignant SEOT present during fifth and sixth decades. The distribution of various tumour types according to age was similar to previous studies (1),(2),(18). This can be explained by the proposal that occasionally over a period of time, few of the benign SEOT can progress to malignant counterpart by marked increase in grades of the epithelial abnormality (1). Majority of the subjects (50 out of 166) were in 41-50 years age group similar to the study observation of Thakkar N and Shah S in which majority of patients were found to be in the age group of 40-59 years (19). However, discordant with the study observation of Pathak P et al., in which major cases were between 20-30 years (9).

Analysis of tumour laterality in SEOTs: Unilateral ovarian involvement is more common than bilateral ovarian involvement in this study. Results are similar to the study observation by Mondal SK et al., whereas Koonings PP et al., and Kar T et al., found a greater number of bilateral tumours 22% and 26.8%, respectively (17),(20),(21), but there is no statistically significant association between laterality and IHC expression of HER2/neu in the current study.

Distribution of serum CA 125 level in SEOTs: In the present study. the mean serum CA 125 level among the malignant tumours was higher 693.19 U/mL and the association between distribution of serum CA 125 level and histopathological diagnosis were statistically significant which is similar to a previous study (22). Serum CA 125 level has been contemplated to be as an independent prognostic marker, which can reflect the tumour burden and also the advanced stage of illness (23).

Distribution of benign, borderline and malignant neoplasms: On analysing the histological diagnosis in the current study, 132 (79.52%) were benign followed by 22 (13.25%) were malignant and 12 (7.23%) were borderline tumours. There are several studies showing similar distribution of SEOTs specifically conducted in South Asia (15).

Distribution of different histopathological types of SEOTs: In the present study, among 166 cases predominantly 84 were of serous (50.6%) type and least 4 (2.41%) cases were of endometrioid type. The above mentioned findings help us to interpret that serous histological type of SEOT was the most common histological type. This can be the main reason for many studies who have encompassed only serous type of SEOTs in their research studies (1). Similar distribution noted in several studies of Asian countries (15).

Distribution of FIGO staging: On evaluating the distribution of FIGO staging among the malignant SEOT of our study, 7 (4.22%) had IA stage followed by 5 (3.01%) had IC stage. This observation is discordant with the study performed by Kurta ML et al., in which stage III tumours is more common (24). But the present study observation is correlating with study done by Mclaughlin JR (25).

Association of HER2/neu IHC expression with clinicopathological parameters: The recent concept of classifying ovarian carcinomas as five broad histological types is: High-grade Serous Carcinoma (HGSC), clear-cell carcinoma, endometrioid carcinoma, mucinous carcinoma, and Low-grade Serous Carcinoma (LGSC), as they differ in their biology, clinical presentation, and chemotherapeutic response. Hence, IHC is useful as robust companion tool for subclassifying ovarian carcinomas (26).

HER2/neu IHC expression among study population: Positive expression rate in this study were 18% which is comparable to the rate of HER2/neu positivity in SEOTs reported in the literature, which ranges from 7-50% (27),(28). Comparing the age group with HER2/neu grading distribution, 20 years had higher proportion of 2+ grading and the difference between HER2/neu expression and distribution of age had statistically significant positive association. In studies who have analysed the same parameters no significant association was documented. Comparing the CA 125 Level with HER2/neu grading distribution, 2+ grading had higher mean of CA 125 Level with 472.19 U/mL and HER2/neu expression had statistically significant positive association with pre-treatment CA 125 levels similar to study done by Arif S et al., (30). Comparing the histopathological diagnosis with HER2/neu grading distribution, malignant had higher proportion of 2+HER2/neu grading thus highlighting the fact that mutation of HER2/neu gene plays a vital role in pathogenesis of tumours as they are the part of signalling pathways occurring intracellularly resulting in cell proliferation and differentiation (9). The difference in HER2/neu grading distribution between different histopathological diagnosis had statistically significant positive association. HER2/neu was negative in all benign cases, higher in grade 2 and 3 malignant tumours in concordance to previous studies (2). Comparing the histological type with HER2/neu positivity distribution, mucinous had higher proportion of HER2/neu positivity with 4.91% followed by serous with 3.57%. This study findings showed concordance with reports of other studies in literature (9).

HER2/neu expression was analysed in all histological types of malignant SEOTs and many of the studies showed that HER2/neu do not show significant expression in non mucinous histological subtype of malignant SEOT. Trastuzumab therapy, an option of choice for mucinous carcinoma with HER2/neu expression. In several studies, overexpression of HER2/neu shows chemotherapy resistance and poor patient survival (9), but the difference in HER2/neu grading distribution between different histological type and FIGO staging was not statistically significant similar to previous studies (29).

HER2/neu an epidermal growth factor receptor family member, overexpressed in 20-30% of ovarian cancer (7). Berchuck et al., first recognised that, HER2/neu overexpression is related to poor survival of patients with late stages of malignant SEOTs which states that patients with HER2/neu overexpression had worse prognosis than patients with normal HER2/neu expression. In addition, patients with high HER2/neu expression did not show complete response to therapy (9).

The most of the findings of this study matching well with proportions and features of many other similar studies. However, the significant positive association between age and HER2/neu IHC expression identified in the present study only, not documented in the literature so far. Currently, very few reported data about HER2/neu protein expression in SEOTs available in India [9-12]. Hence, this proposed study is performed to evaluate HER2/neu status in patients with SEOTs (9).

Limitation(s)

Limitation of the study was lesser number of borderline and malignant SEOTs in the study population, analysis of larger samples of these types would have been adding more value to the results.

Conclusion

The proposed study emphasised the high and consistent IHC expression of HER2/neu in malignant SEOTs and also confirmed its statistically significant positive association with age, CA 125 level and histological diagnosis, but there is no significant association with, size, laterality, histological type and FIGO grading of SEOTs. HER2/neu also had higher IHC expression in malignant tumours, thus emphasising its carcinogenic role and helps in the diagnostic differentiation of benign and borderline tumours with malignant potential from actual malignant tumours. It also paves a better way for understanding the biological nature of SEOTs, to modify treatment modalities and can be a therapeutic target in future.

References

1.
Naik PS, Deshmukh S, Khandeparkar SG, Joshi A, Babanagare S, Potdar J, et al. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study. Journal of Mid-life Health. 2015;6(4):178. [crossref] [PubMed]
2.
Sylvia MT, Kumar S, Dasari P. The expression of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2-neu, p53 and Ki-67 in epithelial ovarian tumors and its correlation with clinicopathologic variables. Indian Journal of Pathology and Microbiology. 2012;55(1):33. [crossref] [PubMed]
3.
Piek JM, van Diest PJ, Verheijen RH. Ovarian carcinogenesis: An alternative hypothesis. Adv Exp Med Biol. 2008;622:79-87. [crossref] [PubMed]
4.
Hall PA, Levison DA. Review: Assessment of cell proliferation in histological material. J Clin Pathol. 1990;43:184-92. [crossref] [PubMed]
5.
Lavin PT, Kanapp RC, Malkasian G, Whitney CW, Berek JC, Bast RC. CA125 for the monitoring of ovarian carcinoma during primary therapy. Obstet Gynecol. 1987;69:223-27.
6.
Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database of Systematic Reviews. 2011;(8):CD007565. [crossref] [PubMed]
7.
Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications. Molecular Biology International. 2014;2014:852748. [crossref] [PubMed]
8.
Ajani MA, Salami A, Awolude OA, Oluwasola AO, Akang EE. The expression status of human epidermal growth factor receptor 2 in epithelial ovarian cancer in Ibadan, Nigeria. Southern African Journal of Gynaecological Oncology. 2016;8(1):05-09. [crossref]
9.
Pathak P, Bamanikar S, Shetty A, Kumar H, Buch A. Histopathological analysis of ovarian tumours and overexpression of HER2/neu in ovarian carcinomas. Indian Journal of Pathology and Oncology. 2019;6(3):440-44. [crossref]
10.
Yadav V, Deshmukh AV, Kumar V, Gangane NM. Expression of HER2/neu receptor in epithelial ovarian cancers: An immunohistochemical pilot study in central India. Indian Journal of Gynecologic Oncology. 2021;19(4):01-06. [crossref]
11.
Gupta S, Mehra M, Khattri J, Madhvi M. A study of her-2/neu oncogene expression in benign and malignant ovarian tumors. Int J Med Res Rev. 2020;8(2):169-75. [crossref]
12.
Grover A, Mohanty M, Dash K. HER-2 neu expression in surface epithelial ovarian tumors and its relationship with clinic-pathological parameters: A pilot study. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2021;10(4):1363-68. [crossref]
13.
International Agency for Research on Cancer, World Health Organization. WHO classification of female genital tumours: Who classification of tumours. 5th ed. Who Classification of Tumours Editorial Board, editor. IARC; 2020.
14.
Gupta D, Lis CG. Role of CA125 in predicting ovarian cancer survival-a review of the epidemiological literature. Journal of Ovarian Research. 2009;2(1):01-20. [crossref] [PubMed]
15.
Verma R, Gupta P, Tiwari N, Lal N, Gupta HP, Srivastava AN. Histological grade, CA-125 Levels and IHC expression of ER/PR. HER-2/NEU, p53 and Ki-67 markers in epithelial ovarian neoplasms: A correlative study. International Journal of Advanced Research. 2017;5(6):235-54. [crossref]
16.
Buchynska LG, Iurchenko NP, Grinkevych VM, Nesina IP, Chekhun SV, Svintsitsky VS. Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers. Experimental Oncology. 2009.
17.
Mondal SK, Banyopadhyay R, Nag DR, Roychowdhury S, Mondal PK, Sinha SK. Histologic pattern, bilaterality and clinical evaluation of 957 ovarian neoplasms: A 10-year study in a tertiary hospital of eastern India. Journal of Cancer research and Therapeutics. 2011;7(4):433. [crossref] [PubMed]
18.
Maheshwari V, Tyagi SP, Saxena K, Tyagi N, Sharma R, Aziz M, et al. Surface epithelial tumours of the ovary. Indian J Pathol Microbiol. 1994;37(1):75-85.
19.
Thakkar N, Shah S. Histopathological study of ovarian lesions. 2015;4(10):1745-49.
20.
Koonings PP, Campbell K, Mishell DR. Relative frequency of primary ovarian neoplasms: A 10 year review. Obstet. 1989;74:921-26.
21.
Kar T, Kar A, Mohapatra PC. Intraoperative cytology of ovarian tumours. J Obstet Gynecol India. 2005;55(4):345-49.
22.
Garg S, Marwah N, Chauhan G, Gupta S, Goyal R, Dahiya P, et al. Estrogen and progesterone receptor expression and its correlation with various clinicopathological parameters in ovarian tumors. Middle East Journal of Cancer. 2014;5(2):97-103.
23.
Laishram S, Gupta V, Bhake A, Wankhede A, Agrawal D. To assess the utility of proliferative marker Ki-67 in surface epithelial ovarian tumor. J Datta Meghe Inst Med Sci Univ. 2019;14:06-10. [crossref]
24.
Kurta ML, Moysich KB, Weissfeld JL, Youk AO, Bunker CH, Edwards RP, et al. Use of fertility drugs and risk of ovarian cancer: Results from a us-based case-control study fertility drugs and ovarian cancer. Cancer Epidemiology, Biomarkers & Prevention. 2012;21(8):1282-92. [crossref] [PubMed]
25.
Mclaughlin JR. Hereditary Ovarian Cancer Clinical Study Group. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: A case-control study. Lancet Oncol. 2007;8:26-34. [crossref] [PubMed]
26.
Amanullah NA, Poothiode U, Vilasiniamma L. Expression of p53 in epithelial ovarian tumors. Indian Journal of Pathology and Microbiology. 2020;63(2):235. [crossref] [PubMed]
27.
Grabowski JP, Harter P, Heitz F, Pujade-Lauraine E, Reuss A, Kristensen G, et al. Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO study group metadatabase. Gynecologic Oncology. 2016;140(3):457-62.[crossref] [PubMed]
28.
Verri E, Guglielmini P, Puntoni M, Perdelli L, Papadia A, Lorenzi P, et al. HER2/ neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Oncology. 2005;68:154-61. [crossref] [PubMed]
29.
Arif S, Samad FA, Syed AS, Khan A, Riaz A, Zahid R. HER2/neu: A prognostic marker for ovarian carcinoma. Middle East Journal of Cancer. 2022;13(3):449-57.

DOI and Others

DOI: 10.7860/JCDR/2023/61283.17547

Date of Submission: Nov 05, 2022
Date of Peer Review: Dec 02, 2022
Date of Acceptance: Jan 04, 2023
Date of Publishing: Feb 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Nov 11, 2022
• Manual Googling: Dec 31, 2022
• iThenticate Software: Jan 02, 2023 (5%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com