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

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Dr Mohan Z Mani

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Believers Church Medical College,
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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."



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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.
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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 : 2021 | Month : July | Volume : 15 | Issue : 7 | Page : EC30 - EC34 Full Version

Expression of Beta-Catenin in Colorectal Carcinoma and its Association with Various Clinicopathological Parameters


Published: July 1, 2021 | DOI: https://doi.org/10.7860/JCDR/2021/48129.15151
Monika Panda, Ranjita Panigrahi, Goutami Das Nayak, Urmila Senapati, Saroj Ranjan Sahoo, Ipsa Mohapatra

1. Postgraduate Student, Department of Pathology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha, India. 2. Professor, Department of Pathology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha, India. 3. Assistant Professor, Department of Pathology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha, India. 4. Professor and Head, Department of Pathology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha, India. 5. Associate Professor, Department of Surgical Oncology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha, India. 6. Associate Professor, Department of Social and Preventive Medicine, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha, India.

Correspondence Address :
Dr. Goutami Das Nayak,
Assistant Professor, Department of Pathology, Kalinga Institute of Medical Sciences, Kushabhadra Campus, KIIT Campus-5, (Near HDFC Bank), KIIT Road, Patia, Bhubaneswar-751024, Odisha, India.
E-mail: goutamidn@gmail.com

Abstract

Introduction: Colorectal Carcinoma (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer related mortality globally. It is a source of concern for researchers worldwide and hence, a lot of emphasis is being given towards early detection and targeted drug therapy to improve the survival rate.

Aim: To study the expression of beta-catenin in colonic polyps, adenomas and CRC and to associate beta-catenin expression with various clinicopathological features.

Materials and Methods: This was a prospective cross-sectional study conducted in the Department of Pathology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India from September 2018 to August 2020. Colonoscopic biopsies, mucinous carcinoma and poorly preserved tissue were excluded. Histopathological study and Immunohistochemistry evaluation of beta-catenin was done. Statistical analysis was done by using appropriate tests. A p-value of less than 0.05 was taken as statistically significant.

Results: Out of 80 cases, 40 cases were benign lesions Non neoplastic polyp and adenoma) and 40 cases were adenocarcinoma. It was observed that benign lesions had maximum cases with preserved membranous expression (36/40) and very few cases (4/40) showed cytoplasmic expression of beta-catenin. But in carcinoma, high cytoplasmic expression was seen in 20/40 (50%) whereas 8/40 (20%) cases had nuclear positivity. Membranous beta-catenin expression was significantly higher in benign lesions than in the malignant lesions (IS:8.75±3.09 versus 4.30±2.70) respectively; (p<0.0001). But cytoplasmic beta-catenin expression was low in benign lesion as compared to malignant lesion (IS: 2.07±3.46 versus 5.35±3.14), respectively; (p<0.0001). However, nuclear beta-catenin expression was extremely low in benign lesions than in malignant lesions (0.08±0.47 versus 1.90±3.49), respectively; (p=0.0016), this difference was statistically significant.

Conclusion: The present study demonstrates the change in beta-catenin expression with gradual transition from predominantly membranous pattern to cytoplasmic or nuclear as we progress from normal colorectal tissues to polyps, benign premalignant lesions and malignant neoplasms. This property of beta-catenin helps in determining malignant potential of various premalignant neoplasms of large intestine which in turn helps in initiating early prophylactic treatment.

Keywords

Adenomatous polyp, Colorectal neoplasms, Membranous expression

The Colorectal Carcinoma (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer related mortality globally (1),(2). As per the World Health Organisation (WHO) GLOBOCAN database, there were 1,849,518 estimated new CRC cases and 880,792 deaths occurred due to CRC (3). The CRC is the fourth most common cause of cancer in males and third most common cause of cancer in females in India (4). The factors influencing outcome in CRC patients are tumour invasion, lymphovascular invasion, status of lymph nodes and serum Carcinoembryonic Antigen (CEA) level (5),(6). Continuous efforts are being put for early diagnosis and targeted therapy for the tumour. Adjuvant therapy is administered basing on individual patient risk and hence, prognostic factors are essential for risk stratification. Adenomatous Polyposis Coli (APC) mutations are acquired early in the pathogenesis of around 80% colon cancers. This leads to cytosolic accumulation of β-catenin which in combination with T cell Transcription Factor (TCF)/Lef1 shuttles to the nucleus where it functions as a transcription factor and promotes cellular proliferation (7),(8). Beta-catenin also has prognostic implications in carcinoma of esophagus, stomach, gall bladder, ovary, endometrium as well as in leukaemia and melanoma (7),(8). This study directs us towards risk stratification, early detection of premalignant lesions and proper categorisation by differential expression of beta-catenin. This was a novel approach towards early and rational targeted therapy of colorectal neoplasms.

Objectives

• To study the expression of beta-catenin in colonic polyps, adenomas and CRC and to compare its expression with that of normal colon.
• Association of beta-catenin expression with various clinicopathological features.

Material and Methods

This was a prospective cross-sectional study conducted in the Department of Pathology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha from September 2018 to August 2020 after approval from Institutional Ethics Committee (IEC No. 90/2018).

Inclusion criteria: Radical excision specimens of histologically confirmed cases of CRC and all specimens of adenoma and colorectal polyps were included.

Exclusion criteria: Colonoscopic biopsies, mucinous carcinoma and poorly preserved tissue were excluded.

Study Procedure

This study included 40 cases of CRC, 20 cases of adenoma and 20 cases of non neoplastic polyps. Along with this, 20 cases of normal colon were also studied. Out of the total cases, 40 were endoscopy guided biopsies and 40 were colectomy specimens. Sample size was calculated after consulting with statistician. Specimens were routinely processed and fixed overnight in 10% buffered formalin. Grossing of the specimens was done as per the recent American Joint Committee on Cancer (AJCC) guidelines (4). Four to five micrometer thick formalin fixed, paraffin embedded tumour sections were stained with Haematoxylin and Eosin (H&E) stain. Histologic examination of tumour type and grade were performed routinely according to criteria outlined in WHO classification of tumours 5th edition, 2019 (3). For colectomy specimen, tumour depth, Lymphovascular Invasion (LVI), Perineural Invasion (PNI) and lymph node status was assessed according to AJCC 8th edition (4).

Evaluation of beta-catenin was done on formalin fixed paraffin embedded tissue sections (4-5 μ thick) on poly L-lysine coated slides by using polymers in two steps (indirect method). Desmoid tumour block served as external positive control whereas normal colon was taken as internal positive control from the same tumour block under study. The IHC staining was done using monoclonal ready-to-use beta-catenin antibody manufactured by Dako (code IS 702). The degree of IHC staining in the tissue sections was scored independently by two pathologists who were blinded to the clinical and pathological data. Staining intensity was graded using a scale of 0-3 as follows:

0: No staining;
1: Weak staining;
2: Moderate staining and
3: Strong staining (9),(10)

The extent of staining was graded on a scale as the following:

0: ≤5%;
1: 6-25%
2: 26-50%
3: 51-75%
4: 76-100% (9),(10)

According to the percentage of the section exhibiting positive staining relative to the entire carcinoma involved area, more than 50% of tumour area showing moderate and strong staining was considered as positive. The intensity and extent scores were multiplied to generate the immunoreactivity score (IS; range, 0-12) for each case.

<6 was considered as low (Negative)
>6 was considered as high (Positive) (11)

Statistical Analysis

Data was entered into Microsoft excel spreadsheet 2010 and analysed using EpiInfo software version 7.1.3. Results were expressed as mean, median, standard deviation, percentages, frequencies and proportions. Statistical analysis was done by Chi-square test, Fisher’s exact test and t-test which were used as tests of association. A p-value of less than 0.05 was taken as statistically significant.

Results

In this study, the total number of subjects were 80 which included 40 cases (50%) of adenocarcinoma, 20 (25%) cases of adenoma and 20 (25%) cases of non neoplastic polyps. The age range of patients was from 1-96 years with mean age being 54.73±21.15 years. Age group of 51-60 years had highest number of cases i.e., 20 (25%) followed by the age range of 61-70 years i.e., 16 (20%). Out of 40 cases of adenocarcinoma, maximum belonged to the age group of 51-60 years and 71-80 years of age with mean age of 61.75±11.62 years, whereas maximum number of adenoma cases belonged to age group of 61-70 years of age.

For statistical analysis, the total cases were divided into two age groups- less than 50 years and more than 50 years. A 42.86% of patients below 50 years had preserved membranous expression and 54.54% of patients above 50 years had preserved membranous beta-catenin expression. Nuclear expression was seen in 28.57% patients with age less than 50 years and in 51.15% patients with age more than 50 years. However, there was no significant association of these results with age (Table/Fig 1). Among the total 40 adenocarcinoma cases, 70% (28 cases) were males and 30% (12 cases) were females with male:female ratio being 2.3:1 (Table/Fig 1).

A 46.42% of males showed preserved membranous beta-catenin expression while it was seen in 58.43% of females. A 53.57% males had increased cytoplasmic beta-catenin expression whereas, 41.66% females had strong cytoplasmic expression. Increased nuclear expression of beta-catenin was seen in 21.42% males and in 25% females. These results were not statistically significant (Table/Fig 1).

Out of 80 cases, there were total number of 60 male patients (75%) and 20 (25%) female patients with male to female ratio being 3:1. Out of 80 cases, 40 cases (50%) were adenocarcinoma. Adenoma with low-grade dysplasia constituted 17 cases (20%) and with high-grade dysplasia constitute 3 cases (5%). Out of 20 cases of non neoplastic polyps, maximum were juvenile polyps, i.e., 10 cases (12.5%) and only one case was hamartomatous polyp (1.25%). Maximum number of adenocarcinoma were located in the right colon 17 cases (42.5%) followed by left colon 14 cases (35%) and minimum in the rectum nine cases (22.5%). A total of 29 cases (72.5%) of adenocarcinoma cases belong to grade I followed by seven cases (17.5%) in grade II and only four cases (10%) of carcinoma belong to grade III. A 45% (18 cases) of carcinoma belong to stage II, 30% (12 cases) belong to stage IIIB and only 5% (02 cases) belong to stage IIIC. LVI was present in 23 cases (57.5%) adenocarcinoma cases and PNI was present in10 cases (25%). A 45% (18) of adenocarcinoma cases had positive metastatic nodes (Table/Fig 2).

There were 45.2% cases in right colon, 35% cases in left colon and 22.5% cases in rectum. High beta-catenin positivity was seen in left colon (21.42%) and rectum (33.33%). These results showed statistically significant association with p-value=0.03 (Table/Fig 2).

According to histological grading, the CRC cases were divided in two groups grade I, II and grade III. A 47.22% of grade I, II tumours had preserved membranous expression while 50% of grade III tumours had increased nuclear expression. High cytoplasmic beta-catenin expression was seen in 52.78% of grade I, II tumours and in 50% of grade III tumours. Increased nuclear expression was seen in 16.66% of grade I, grade II tumours and 25% of grade III tumours. Membranous, cytoplasmic and nuclear expression of beta-catenin did not show any statistically significant association with histological grade of CRC (Table/Fig 2).

Based on staging, tumours were categorised into two groups- Stage I, II and Stage III. A 36.36% tumours of Stage I, II had membranous beta-catenin expression while the same was observed in 72.22% cases of stage III. Increased cytoplasmic expression was found in 63.63% of stage I, II tumours and in 21.77% of stage III tumours. A 27.27% cases of stage I, II have high nuclear beta-catenin expression while no case among stage III tumours had nuclear expression of beta-catenin. These differences were statistically significant with p-value=0.02 (Table/Fig 2).

Preserved membranous beta-catenin expression was seen in 77.77% cases with nodal metastasis. High cytoplasmic expression was seen in 22.22% cases with nodal metastasis. Nuclear expression was seen in 11.11% cases with nodal metastasis. No statistically significant association was observed between beta-catenin expression and lymph node metastasis (Table/Fig 2).

A 23 cases of carcinoma showed vascular invasion and 10 cases showed perineural invasion. A 47.82% of tumours showing LVI and 50% of tumours showing PNI had preserved membranous beta-catenin expression. A 52.17% tumours with LVI and 50% of tumours with PNI had cytoplasmic expression. A 13.04% of tumours with LVI and 10% of tumours with PNI had nuclear beta-catenin expression. There was no statistically significant association found between LVI with beta-catenin expression and PNI with beta-catenin expression (Table/Fig 2).

Out of 80 total cases, 40 cases were benign lesions (Non neoplastic polyps and adenoma) and 40 cases were adenocarcinoma. We observed that maximum benign lesions had preserved membranous expression (36/40); very few cases (4/40) showed cytoplasmic expression of beta-catenin and only one case of adenoma with high grade dysplasia showed nuclear positivity. But in carcinoma, preserved membranous expression was in 20/40 (50%), high cytoplasmic expression was in 20/40 (50%), whereas 8/40 (20%) cases had nuclear positivity. Membranous beta-catenin expression was significantly higher in benign lesions than in malignant lesions. (IS:8.75±3.09 versus 4.30±2.70), respectively; (p<0.0001). But cytoplasmic beta-catenin expression was low in benign lesion as compared to malignant lesion (IS: 2.07±3.46 versus 5.35±3.14), respectively (p<0.0001).

However, nuclear beta-catenin expression was extremely low in benign lesions than in malignant lesions (0.08±0.47 versus 1.90±3.49), respectively; (p<0.0016) This difference was statistically significant (Table/Fig 3).

Discussion

The various patterns of IHC expression of beta-catenin and its association with age, sex, site, histological grade, pathological stage, LVI, PNI and LN metastasis were studied.

Beta-catenin has a major role in development of CRC. Its function is controlled by Wingless-related integration site (Wnt) signaling pathway (12). Normally beta-catenin is degraded by APC-beta catenin complex, thus avoiding its intracellular accumulation (13),(14).

Mutations of APC and beta-catenin genes cause over accumulation of intracellular beta-catenin level which translocates to nucleus causing activation of transcription factor and uncontrolled growth of tumour cells.

Out of 40 cases of adenocarcinoma, maximum belonged to the age group of 51-60 years (27.5%) and 71-80 years (27.5%) of age with mean age of 61.75±11.62 years, whereas maximum number of adenoma cases belonged to age group of 61-70 years of age (25%). In this study, we found that patients with >50 years of age showed high cytoplasmic and nuclear expression of beta-catenin. But these results were statistically insignificant. Abdul rahaman ZA et al., similarly found that beta-catenin was frequently expressed in >50 years of age (14). Gao ZH et al., also found that >60 years of patients had more cytoplasmic and nuclear beta-catenin expression (10).

There was a male preponderance among the patients with adenocarcinoma in this study with male to female ratio being 2.3:1. Males had increased cytoplasmic beta-catenin expression while females had a higher nuclear expression of beta-catenin. No significant association was found between beta-catenin expression and gender of patients. Gao ZH et al., and Yoshida N et al., had findings similar to this study (10),(15).

A 42.5% cases of adenocarcinoma were located in right colon and 35% in left colon. Right colon carcinomas had preserved membranous expression whereas increased nuclear and cytoplasmic expression was seen in rectal carcinomas. This result was statistically significant with p-value=0.03. Present study findings were agreeable with Gao ZH et al., (10); but showed discordant results with studies by Abdulrahaman ZA et al., and Wantisawan W et al., (14),(16).

In the present study, out of 40 adenocarcinoma cases, 29 had histological grade I, seven had grade II and only four had grade III. No significant association was found between beta-catenin expression and histological grading of tumour. Wantisawan W et al., had maximum grade I tumours having highest nuclear beta-catenin expression (16). Gao ZH et al., found increased cytoplasmic expression in grade-I and II tumours (10).

A 45% of adenocarcinoma cases in the study had pathological stage II, 30% had stage IIIB, 10% had stage IIIA and 5% had stage IIIC. There was statistically significant association of beta-catenin expression with pathological stage with p-value=0.02. Wantisawan W et al., found that maximum tumours had stage II having highest nuclear beta-catenin positivity (16). Abdulrahaman ZA et al., found low cytoplasmic expression of beta-catenin in stage I and II tumours than in those of stage III and IV (14). Gao ZH et al., found more number of cases with preserved membranous expression along with high nuclear positivity in tumours of stage I and II (8),(10). These studies were discordant with our study.

Nodal metastasis was seen in 18 cases of adenocarcinoma. However, there was higher cytoplasmic and nuclear beta-catenin expression in cases without nodal metastasis. But no significant association was observed. Gao ZH et al., and Wanistsawan W et al., had coherent results with this study (10),(16). On the contrary, Abdulrahaman ZA et al., found that node positive cases had higher beta-catenin expression than node negative patients (14).

Vascular invasion was present in 23 cases of carcinoma. A 77.77% of patients with vascular invasion had preserved membranous expression and high cytoplasmic expression. There was similar expression of membranous and cytoplasmic beta-catenin in cases both with and without perineural invasion. Gao ZH et al., observed that only 3 out of 182 cases showed vascular invasion (10). All these cases showed membranous expression and only one case had high cytoplasmic expression. However, this was not consistent with the study.

It was observed that most of the benign lesions (36/40) had preserved membranous expression (Table/Fig 4) and very few cases (4/40) had cytoplasmic expression of beta-catenin. Only one case of adenoma with high-grade dysplasia showed cytoplasmic beta-catenin positivity. Among carcinoma cases, preserved membranous expression was seen in 50% cases (Table/Fig 5), high cytoplasmic expression in 50% whereas nuclear positivity was observed in 20% cases (Table/Fig 6).

Membranous beta-catenin expression was significantly higher in benign lesions than in the malignant lesions. (IS:8.75±3.09 versus 4.30±2.70) respectively; (p<0.0001). But cytoplasmic beta-catenin expression was low in benign lesion as compared to malignant lesion (IS): 2.07±3.46 versus 5.35±3.14), respectively; (p<0.0001). However, nuclear beta-catenin expression was extremely low in benign lesions than in malignant lesions (0.08±0.47 versus 1.90±3.49) respectively; (p<0.0016). This difference was statistically significant (Table/Fig 3).

Bhattacharya I et al., observed statistically significant correlation between IHC score and localisation of beta-catenin showing gradual shift from membrane localisation to nuclear positivity (p<0.004) (17). This study was concordant with present study. Gao ZH et al., observed that membranous expression was exclusively seen in tumour center whereas in invasive fronts, nuclear beta-catenin level was significantly increased (10).

Limitation(s)

Lack of significant association between beta-catenin expression and grading of tumour may be due to presence of lesser number of grade III tumours in our study.

Conclusion

In the present study, beta-catenin nuclear expression was found to be high in left colon and rectum. Beta-catenin scoring was found to be have statistically significant difference with stage of tumour. High cytoplasmic and nuclear positivity was observed more in early stages of tumour. Membranous expression of beta-catenin was exclusively preserved in benign lesions whereas most of the malignant lesions showed cytoplasmic and/or nuclear expression. This was statistically significant. To conclude, the study demonstrated the gradual transition in expression of beta-catenin from a predominantly membranous expression to subsequent positivity in cytoplasmic or nuclear location as it progressed from normal colorectal tissue to polyps and benign, premalignant lesions to malignant neoplasms.

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DOI and Others

10.7860/JCDR/2021/48129.15151

Date of Submission: Dec 16, 2020
Date of Peer Review: Jan 25, 2021
Date of Acceptance: Apr 15, 2021
Date of Publishing: Jul 01, 2021

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? No
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
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• iThenticate Software: May 07, 2021 (21%)

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