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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
E-cadherin Immunoexpression Patterns in Gastric Carcinoma Histological Subtypes: A Hospital-based Descriptive Study
Correspondence Address :
Dr. T Divyagna,
48-42/1, Beside Janahitha Dental Clinic, Ganeshnagar, Chintal, Hyderabad, Telangana, India.
E-mail: divyagnat@gmail.com
Introduction: Gastric carcinoma is the second common Gastrointestinal (GIT) malignancy. Based on Global Cancer Observatory (GLOBOCAN) 2020 data, it is the 5th most common neoplasm and the 4th most common cause of death. Epithelial-cadherin (E-cadherin) is a transmembrane glycoprotein which plays a crucial role in maintaining cell-cell adhesion. Loss of E-cadherin contributes to enhanced invasion and metastasis in human cancers.
Aim: To study E-cadherin immunohistochemical expression in tumour cells and its association with gastric carcinoma histotypes.
Materials and Methods: It is a hospital-based descriptive study conducted at Department of Pathology, Osmania General Hospital, Hyderabad, Telangana, India from January 2010 to December 2012 as it was my dissertation. Routine histopathology and immunohistochemistry for E-cadherin were done on the sections. E-cadherin immunohistochemical staining and expression in tumour cells were evaluated according to the study by Jawhari A et al., Scores (0-3) were applied: 0-No staining; 1-Only cytoplasmic staining; 2-Cytoplasmic and membranous staining in the same case, 3-Normal membranous immunoexpression. Staining was evaluated based on absence of membranous expression scores (0 and 1) versus the presence of membranous expression (scores 2 and 3). Statistical analysis of the data was done by Chi-square test using Epi Info software.
Results: Total 70 cases were studied, of which 48 were gastric biopsies and 22 were gastrectomies. Gastric adenocarcinomas were classified as intestinal 40 cases (57.14%) and diffuse 30 cases (42.85%) according to Lauren’s classification. Membranous staining of E-cadherin was seen in 34/40 cases (85%) of intestinal gastric cancer and 9/30 cases (30%) of diffuse intestinal cancer whereas non membranous or absent E-cadherin was seen in 6/40 cases (15%) of intestinal gastric cancer and 21/30 cases (70%) of diffuse gastric cancer. In this study, significant association was found between membranous E-cadherin expression (score 2 or 3) and intestinal histotype and absence of membranous expression (scores 0 or 1) and the diffuse histotype of gastric cancer.
Conclusion: Normal gastric mucosa shows strong membranous E-cadherin positivity. There is a change in the pattern of E-cadherin expression from membranous in intestinal type gastric adenocarcinoma to non membranous expression of E-cadherin in diffuse type of gastric carcinoma.
Adenocarcinoma, Epithelial cadherin, Immunohistochemistry
Gastric carcinoma is the fourth most common cause of cancer related deaths worldwide, according to GLOBOCAN data 2020 (1). The most common histological type is adenocarcinoma which accounts for about 90-95% of gastric cancer (2),(3). Gastric adenocarcinoma is histologically classified into intestinal and diffuse type by the Lauren classification system (4). The most important prognostic factor includes stage followed by histologic type (5). Patients in the same stage and histologic type may have varied prognosis, therefore additional parameters have to be identified in order to better classify the biological subsets of the disease (6). Early symptoms of both types of gastric adenocarcinoma resemble those of chronic gastritis and peptic ulcer disease including dyspepsia, dysphagia and nausea. As a result, these tumours are often diagnosed at advanced stages when symptoms such as weight loss, anorexia, early satiety, anaemia and haemorrhage trigger further diagnostic evaluation. Gastric cancer is more common in lower socio-economic groups and in individuals with multifocal mucosal atrophy and intestinal metaplasia. Gastric dysplasia and adenomas are recognisable precursor lesions associated with gastric adenocarcinoma (7).
A better understanding of the molecular basis of cancer has led to the development of molecular targeted therapies that interferes with signalling cascade involved in cell differentiation, proliferation, and survival.
E-cadherin (CDH1) is a Ca2+ dependent cell-to-cell adhesion molecule located on long arm of chromosome 16 (q22.1) (8),(9). It forms a multiprotein complex with catenins (α and β-catenin) which interact with the actin cytoskeleton (8). It is a 120 kD transmembrane glycoprotein that is responsible for calcium-dependent intercellular adhesion by homotypic interactions (10),(11),(12). It is expressed on the surface of epithelial cells, at the level of the intercellular junction and is important for establishing cell polarity, maintaining epithelial integrity and cellular differentiation (13),(14). It is an intercellular adhesion molecule which plays an essential role in the complex process of invasion and metastasis (15),(16),(17),(18). Mutations in the CDH1 gene have been observed in 50% of sporadic diffuse-type gastric cancers (19),(20). Altered E-cadherin expression due to genetic mutations is commonly seen in diffuse type gastric carcinomas and emphasises the significance of E-cadherin in early diffuse type tumours (21),(22).
Hence, the present study aimed to study the pattern of E-cadherin expression in gastric adenocarcinoma by immunohistochemistry and to characterise gastric carcinoma histotypes based on E-cadherin immunoexpression.
This hospital-based descriptive study was done in the Department of Pathology, at Osmania General Hospital, Hyderabad, Telangana, India, from January 2010 to December 2012. Out of 70 specimens, of which 48 endoscopic biopsies and 22 gastrectomies, which were confirmed as adenocarcinoma in histopathological examination were included in the study. No ethical issues were involved in the study, as it is not involving subjects directly and being a part of dissertation work, the study was approved by the Head of Department.
Inclusion criteria:
• Histopathologically confirmed gastric adenocarcinoma was included.
• No prior treatment.
• Adequate tumour tissue for analysis.
• Complete clinicopathologic data (age, sex, histopathological diagnosis) was collected.
Exclusion criteria: Cases with extensive tumour necrosis without sufficient viable tumour cells for an accurate evaluation of the immunohistochemical results were excluded.
Study Procedure
Gastrectomy’s and small biopsy specimens were received in 10% neutral buffered formalin. Detailed clinical history of each case including age, gender, clinical presentation, nature of specimen, location of the tumour were noted. The specimens were grossed, and sections were taken from representative sites. The sections were then processed in automated tissue processor and embedded in paraffin wax, 4 microns thick sections were cut, stained with Haematoxylin and Eosin (H&E), mounted and then examined by light microscopy. These H&E stained slides were studied for the tumour histology and classified into intestinal and diffuse according to Lauren’s classification (4).
In addition, 4 μm sections were cut from a paraffin block of tumour tissue and taken on a poly-L-lysine coated glass slide for Immunohistochemistry (IHC) to detect E-cadherin expression. E-cadherin immunostaining was done with monoclonal mouse anti-human E-cadherin clone NCH-38 (DAKO). Staining was done according to the manufacturer’s protocol.
Gastric and colonic normal mucosal sections away from the site of the tumour, and normal gastric glands between tumour cells, were used as positive controls. The fibroblasts and lymphocytes in these distant samples and inside tumour areas were considered as negative controls.
The slides are then examined under microscope and intensity of E-cadherin staining was graded according to study by Jawhari A et al., (23).
Scoring and Evaluation
Abnormal expression:
Score 0- No staining.
Score 1- Cytoplasmic staining without membranous staining.
Score 2- Cytoplasmic and membranous staining in the same case.
Normal expression:
Score 3- Normal membranous immunoexpression.
Jawhari scores were evaluated as absence of membranous expression (scores 0 and 1) versus the presence of membranous expression (scores 2 and 3) in intestinal and diffuse adenocarcinoma (23),(24).
Statistical Analysis
Statistical analysis of the data was done by Chi-square test using Epi Info software. The p-value is 0.00001. Probability value of <0.05 was considered significant.
Out of 70 cases, which were confirmed as gastric adenocarcinoma, out of which 48 were gastric biopsies and 22 were gastrectomy specimens. The age of the patients ranged from 25-75 years and majority of cases 30 (42.85%) were seen in 5th to 6th decade (Table/Fig 1). Out of 70 cases, 48 (68.57%) were males, and 22 (31.42%) were females with male to female ratio of 2.18:1 (Table/Fig 1). Most of the cases 38 (54.28%) in the present study were located in the pyloric antrum (Table/Fig 2). The common symptom observed in our study was weight loss (40%) followed by anorexia (34.2%) (Table/Fig 3). Of the total 70 cases, 40 cases (57.14%) are intestinal and 30 cases (42.85%) are diffuse type (Table/Fig 4). Most of the intestinal type gastric carcinoma 24/40 (60%) showed score 3 E-cadherin positivity, whereas diffuse type gastric carcinoma 14/30 (47%) showed score 0 E-cadherin staining (Table/Fig 4). Membranous staining of E-cadherin was seen in 34 cases (85%) of intestinal gastric cancer, whereas non membranous staining of E-cadherin was seen in 21 cases (70%) of diffuse gastric cancer (Table/Fig 5),(Table/Fig 6),(Table/Fig 7),(Table/Fig 8),(Table/Fig 9).
E-cadherin, a transmembrane glycoprotein has an essential role in the homotypical cell-cell adhesion and involved in the complex process of invasion and metastasis (25),(26),(27). Reduced or absent expression of E-cadherin causes dissociation of the cells by loosening of cell junctions and in a way acts as a tumour suppressor (28). According to many studies, the role of E-cadherin in carcinogenesis is not only limited to invasion and metastasis, but also involved in modulating intracellular signalling, and thus promoting tumour growth (29),(30). The presence or absence of membranous staining is the most valuable criteria in evaluating E-cadherin expression and gastric carcinoma histotypes (31),(32),(33). In the present study, we want to see the association of E-cadherin membranous or non membranous expression with gastric carcinoma histotypes in our local population.
The Jawhari scoring system is an effective qualitative approach to evaluate E-cadherin expression in gastric cancer (23). Abnormal expression of E-cadherin has been found to have a wide range of variation in different series, from 24-75% (23),(25),(34). Abnormal expression corresponds to score 0,1,2 of Jawhari scoring (23) which implies to absent or cytoplasmic or cytoplasmic and membranous staining. Abnormal expression was found in 16/40 cases (40%) of intestinal type and 26/30 cases (86.65%) of diffuse type (Table/Fig 4). The present study findings correlate well with observations of Almeida PR et al., and Zhou YN et al., Sundarama S et al., Sisodiya N and Jagani R; Sridevi C et al., Kishan J and Moula MC; Sadanandan A and Arunraj CN (Table/Fig 10) (6),(24),(25),(35),(36),(37),(38), so abnormal expression was found in total 42 cases (60%) of our samples including both intestinal and diffuse types. Normal expression corresponds to score 3, which implies membranous staining seen in 24/40 cases (60%) of intestinal type gastric cancer and 4/30 cases (13.33%) of diffuse type gastric cancer.
Most important consideration in E-cadherin expression is presence of E-cadherin in cellular membranes (Jawhari A et al., (23) scores 2 or 3) versus absence (scores 0 or 1) of E-cadherin in cellular membranes, which is the site where this adhesion molecule acts.
In present study, correlation was found between membranous E-cadherin expression (score 2 or 3) and the intestinal histotype 34 cases (85%) and absence of membranous expression (scores 0 or 1) and the diffuse histotype 21 cases (70%) of gastric cancer. Similar expression was also found in studies done by Almeida PR et al., Sridevi C et al., Carpenter PM et al., Lazar D et al., and Wu ZY et al., (Table/Fig 11) (24),(37),(39),(40),(41).
The identification of E-cadherin in the cytoplasm (abnormal expression) and not on the membrane (normal expression) is consistent with the notion that loss of membrane E-cadherin promotes tumour disaggregation and dissemination. Abnormalities of E-cadherin implicated in tumour spread include complete absence of expression, which prevents any E-cadherin-mediated adhesion between affected tumour cells, and mutation of the E-cadherin molecule (41),(42),(43).
Limitation(s)
In the present study, expression of E-cadherin was studied based on histological subtype of gastric carcinoma. E-cadherin expression based on histological grade of the tumour and lymphnode status was not done in the present study.
Immunohistochemical expression of E-cadherin showed membranous positivity in normal gastric mucosa. In gastric carcinoma, the expression gradually changed from membranous to cytoplasmic or absent staining from intestinal to diffuse histological subtypes. Since abnormal expression of E-cadherin is associated more with diffuse type gastric cancers. This can be used as a negative prognostic factor, if tumour staging, grading and lymph node status are correlated with the IHC expression and histological subtypes in future studies. Adequate patient follow-up to allow comparison of prognosis and survival rate between tumour subgroups and their IHC profiles, needs to be done in future studies.
DOI: 10.7860/JCDR/2023/60578.17542
Date of Submission: Oct 04, 2022
Date of Peer Review: Nov 19, 2022
Date of Acceptance: Jan 19, 2023
Date of Publishing: Feb 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? No
• 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
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