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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
Original article / research
Full Version
Role of CD10 as a Prognostic Marker in Invasive Breast Carcinoma
Correspondence Address :
Subitha Kandamuthan,
Associate Professor, Department of Pathology, Government Medical College, Thrissur-680596, Kerala, India.
E-mail: subitha@rediffmail.com
Introduction: Stromal markers have been proved as important markers in assessing the prognosis of invasive breast cancer. Cluster of Differentiation (CD)10 is a cell surface enzyme with metalloendopeptidase activity which is expressed in stroma of various epithelial malignancies.
Aim: To estimate the expression of stromal CD10 expression in breast carcinoma and it’s association with other prognostic markers like Oestrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal growth factor Receptor 2 (HER2-neu), Ki-67and tumour grade.
Materials and Methods: This study was a hospital based cross-sectional study conducted on 50 cases of breast cancer received in histopathology laboratory of the Department of Pathology, Government Medical College, Kottayam during a period of two years from July 2015 to June 2017. Adequate representative sections were taken and Haematoxylin and Eosin (H&E) staining was done. Immunohistochemistry (IHC) of the tissue sections was done by ER, PR, HER2-neu, Ki-67 and CD10. Descriptive statistics was used for the presentation of data showing number and percentages. Mantel-Haenzel (MH) Chi-square test was used for finding the association between CD10 and other prognostic markers of breast carcinoma like ER, PR, HER2-neu and Ki-67.
Results: In this study, all patients were females with mean age of 57.26 years. CD10 was found associated with tumour grade with p-value=0.013. The association of CD10 with ER, PR, HER2-neu was statistically insignificant. Though the association of CD10 and Ki-67 was observed (MH Chi-square value was 0.015), but it was not statistically significant (p-value=0.903).
Conclusion: A statistically significant association of CD10 with increasing tumour grade was observed and the association of CD10 with ER, PR, HER2-neu and Ki-67 was not significant.
Breast carcinoma, Cluster of differentiation 10, Immunohistochemistry, Prognosis, Stromal marker
Breast cancer is one of the common causes of death due to cancer in women worldwide. According to Indian Council of Medical Research (ICMR), 1.67 million new breast cancer cases were diagnosed in 2012 worldwide. Incidence of breast cancer has overtaken cervical cancer and is the leading cause of cancer death in urban India with an annual incidence of more than 1.5 lakh cases (1). Invasive breast carcinoma No Special Type (NST) is the most common type of breast carcinoma (2). The routine immunohistochemical markers used in the evaluation of breast cancer specimens are ER, PR, and HER2-neu. These markers are prognostic indicators and they also decide further clinical management of breast cancer. Many studies have identified that the interaction between stromal components and tumour cells in breast carcinomas is a critical step in tumour progression (3),(4),(5). Tumour stroma plays an important role in tumour invasion and metastasis (6). Stromal markers have shown to have an important role in assessing the prognosis and treatment of breast carcinoma.
CD10, a cell surface metalloproteinase, which is usually called Common Acute Lymphoblastic Leukemia Antigen (CALLA) was originally described as a cell surface marker for sub classification of acute leukaemias and malignant lymphomas. CD10 has been demonstrated in a variety of normal and neoplastic tissues. This marker has been routinely used in histopathological diagnosis of non haematopoietic tumours (7). Many studies have been done to find out correlation of stromal CD10 expression with other prognostic markers of breast carcinoma. They have proved an association between stromal CD10 expression and poor prognosis (8),(9),(10),(11). Most of these studies correlated the expression of CD10 with ER, PR and Her2-neu. Only few studies were done to find out association of CD10 with Ki-67.
The present study was done to assess the magnitude of stromal expression of CD10 in invasive breast carcinomas and to evaluate prognostic significance of stromal CD10 expression by its association with proven prognostic markers of breast carcinoma like ER, PR, HER2-neu and Ki-67 expression and tumour grade.
This study was a cross-sectional study in a tertiary care hospital of Government Medical College Kottayam, including mastectomy specimens received in histopathology laboratory during a period of two years from July 2015 to June 2017. Trucut breast biopsies and post chemotherapy mastectomy specimens were excluded from the study. The study was approved by Institutional Review Board (IRB:99/2015).
Formal written informed consent was not availed as it was waived by the institutional Research Committee. Formalin fixed, paraffin-embedded tissue specimens were cut into 5 mm-thick sections, and stained with Haematoxylin and Eosin (H&E). Histopathologic evaluation was done and classification of tumours was done based on World Health Organisation (WHO) classification (2). Every case of invasive breast carcinoma of no special type during the period of two years was selected which accounted for 50 cases. Nottingham modification of Scarff-bloom-Richardson-Method was utilised for histologic grading of the tumours (12).
Staging was based on the Tumour Node Metastasis (TNM) system adopted by both the Union for International Cancer Control (UICC) and the American Joint Commission on Cancer (AJCC) and was used for staging of tumours (13). Immunohistochemistry (IHC) was used to assess the expression of ER, PR, HER2-neu, Ki-67 and CD10 (Table/Fig 1). The immunohistochemistry was done on formalin-fixed paraffin-embedded breast tissue blocks with normal breast tissue serving as positive control for ER and PR. Tissue sections of HER2-neu positive breast cancer were kept as positive control for HER2-neu and myoepithelial cells of normal breast tissue served as positive control for CD10. ER, PR and HER2-neu was reported according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) Protocols by two Pathologists independently to exclude observation bias (14),(15).
When <10% tumour stromal cells showed staining, CD10 immunostaining was considered as negative, weak (either diffuse weak staining or weak or strong focal staining in less that 30% of stromal cells per core) and strong staining (when 30% or more of the stromal cells were present).
Allred scoring system was used to grade ER and PR which is a semi–quantitative system that takes into account the proportion of positive cells (scored on a scale of 0-5) and staining intensity (scored on a scale of 0-3) (16). The proportion and staining were then added to produce total scores of 0 or 2 through 8. A score of 0-2 was regarded as negative and 3-8 as positive. Tumours having 1% or higher number of cells, nuclear-positive stained for ER and PR are considered positive and if <1% of the tumour cells demonstrated labeling for the hormonal receptors or had an Allred score of 0 to 2, they were labelled as negative.
HER2-neu scoring was done according to the ASCO/CAP guidelines (15). Score 0 and 1 were considered negative. Score 2 was taken as equivocal which had to be confirmed by Fluorescence In-situ Hybridization (FISH). Hence, HER2-neu 2+ was taken as negative along with HER2-neu 0 and 1+. Only 3+ on IHC was taken as positive in this study. Ki-67 labeling index is the percentage of cells showing Ki-67 positive nuclear immunostaining. A 500 tumour cells were assessed and Ki-67 values were expressed as the percentage of positive cells in each case. Cases showing more than 15% positive nuclei were classified as high Ki-67 expression, and those with less than 15% were classified as low Ki-67 expression (17).
Statistical Analysis
Analysis of data was done performing descriptive statistics using number and percentages as well as inferential statistics with Mantel-Haenzel (MH) Chi-square test. Association between CD10 and ER, PR, HER2-neu, Ki-67 and tumour grade was taken as statistically significant when p-value was less than 0.05.
In this study, all patients were females and mean age of the patient was 57.26 years (range 33-80 years). CD10 immunostaining was done on all 50 cases. Of these, 41 (82%) cases showed CD10 positive and 9 (18%) cases were CD10 negative. Out of these, 41 positive cases, 22 (44%) cases were strong positive and 19 (38%) cases were weak positive (Table/Fig 2). Both strong and weak CD10 positive cases were evaluated for its association with ER, PR, HER2-neu and Ki-67.
Out of 50 cases of breast carcinoma, 31 (62%) were positive for ER. Of the ER +ve cases, 80.6% cases were positive for CD10 and 19.4% cases were negative for CD10. Out of the 19 ER –ve cases, 84.2% cases were positive for CD10 (Table/Fig 3). Sensitivity of CD10 compared to ER was 80.65% and specificity was 15.68%. Mantel-Haenzel Chi-square test was 0.099 with a p-value of 0.752 which was statistically not significant.
Out of 50 cases, 29 (58%) were PR +ve. Of the 29 PR +ve cases, 24 (83%) were CD10 +ve. Among the 21 PR –ve cases, 17 cases (81%) were CD10 +ve (Table/Fig 4). Sensitivity of the CD10 positive was found to be 82.76% and specificity 19%. Mantel-Haenzel Chi-square test was 0.026 with a p-value of 0.87 which was statistically not significant.
Out of 50 cases, 23 (46%) were HER2-neu -ve score 0 or 1, 7 (14%) were HER2-neu +ve score 2 and 20 (40%) were HER2-neu +ve score 3. Of the score 3 HER2-neu +ve cases, 16 (80%) were positive for CD10. Of the 23 HER2-neu -ve cases, 21 (91.3%) were positive for CD10 (Table/Fig 5)a. Seven (14%) HER2-neu +ve cases with score 2 were excluded from the study as these cases were to be confirmed by FISH. Mantel-Haenzel Chi-square test was 1.11 with p-value of 0.292 which was statistically not significant (Table/Fig 5)b.
Of the 50 cases, 8 (16%) were triple negative cases. Among them, CD10 was positive (strong and weak) in 7 (87.5%) cases (Table/Fig 6). Of the 45 Ki-67 +ve cases, CD10 was positive in 37 (82.2%) cases (Table/Fig 7) which accounted for sensitivity of 82.2. Mantel-Haenzel Chi-square test was 0.015 with a p-value of 0.903. There was a positive association between CD10 and high Ki-67 but it was not statistically significant.
Of the 32 cases of higher grade tumours, 28 (87.5%) were CD10 positive (strong or weak). Among the 5 lower grade tumours, 2 (40%) showed CD10 positivity (Table/Fig 8). Mantel-Haenzel Chi-square test was 6.19 with p-value of 0.013 which was statistically significant.
In the present study, CD10 positive cases accounted for 41 (82%) cases and 9 (18%) cases were CD10 negative. Out of these positive cases 22 (44%) cases were strong positive and 19 (38%) cases were weak positive. This is similar to studies by Rizk AM et al., and Puri V et al., (5),(10).
Tumour grade according to Nottingham’s grading could be assigned to only 37 cases. Among them, 81.08% were CD10 positive (strong or weak). This indicates that CD10 is a very sensitive test among the graded tumours. Association between CD10 expression and higher grade of tumour was statistically significant (p-value=0.013). Studies by Louhichi T et al., Makretsov NA et al., Puri V et al., and Hosni HN et al., showed a positive correlation between CD10 immunostaining and tumour grade (3),(8),(10),(18). But the study by Raziq AH and Masoud SM, showed no significant correlation between tumour grade and CD10 immunostaining (9).
There was no significant association between CD10 and ER and PR. Both ER, PR positive and ER, PR negative tumours showed a CD10 strong positivity. Studies by Puri V et al., showed a negative correlation of CD10 with ER and PR. Study by Makretsov NA et al., showed a significant correlation of CD10 with negative ER status but no significant correlation with PR. Sensitivity of CD10 compared to ER was 80.65% and specificity 15.68% (Table/Fig 3). Though the sensitivity of the test was found to be high, specificity was found to be low. Thus, this can be used as good test for screening purposes but a poor reliable test for excluding the cases.
In the present study, a significant association between CD10 and HER2-neu staining was not seen. In a study by Chattopadhyay M et al., a negative correlation between CD10 and ER and PR status was seen, which was not statistically significant and no correlation was found between CD10 and HER2-neu (19). Study by Puri V et al., showed a positive correlation of CD10 with HER2-neu but Makretsov NA et al., found that there was no correlation between CD10 and HER2-neu (8),(10).
There were eight triple negative cases. CD10 was positive in 87.5% of the cases. This shows a strong association of CD10 positivity with triple negative status but it was not stastically significant. A similar association was found in a study by Kamal M et al., (20). In their study, the triple negative cases showed a higher CD10 positivity as compared to the non triple negative cases which was statistically not significant. Of the 45 Ki-67 +ve cases, CD10 positivity was seen in 82.2% cases. An association was established between high Ki-67 and CD10 but it was not statistically significant. Positive correlation of CD10 with high Ki-67 was found in studies by Puri V et al., and Chattopadhyay M et al., (10),(19). Only few studies are available correlating CD10 with Ki-67. Lack of significance was attributed to limited number of cases in the study by Chattopadhyay M et al., (19).
Limitation(s)
This study was done including 50 cases of breast carcinoma. More relevant inferences can be made if the study is done in a larger number of cases. FISH was not available for evaluation of score HER2-neu positive cases.
In the present study, 82% of breast carcinoma cases showed CD10 positivity. CD10 stromal overexpression positively associated with increasing tumour grade but there was no significant correlation could be obtained between CD10 and ER, PR and HER2-neu status. CD10 stromal overexpression was significantly associated with triple negative cases and high Ki-67. Since, this marker was associated with tumour grade, it can be included in the routine panel of IHC markers as a prognostic marker. It is already proven by various studies that stromal CD10 expression is associated with more aggressive behavior in various epithelial malignancies (7). Further studies including a larger number of cases and all histopathological types of breast carcinoma are needed to find out the definite role of stromal CD10 expression in targeted therapies.
DOI: 10.7860/JCDR/2022/51661.16063
Date of Submission: Jul 30, 2021
Date of Peer Review: Sep 29, 2021
Date of Acceptance: Dec 01, 2021
Date of Publishing: Mar 01, 2022
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? NA
• For any images presented appropriate consent has been obtained from the subjects. NA
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