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

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On Sep 2018




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"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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Lucknow
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On Aug 2018




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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.
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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.
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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 : EC11 - EC14 Full Version

A Study on the Assessment of Galectin-3 Expression in Colorectal Neoplasm and its Relationship with Tumour Stage, in Tertiary Care Hospital, Kolkata, India


Published: July 1, 2021 | DOI: https://doi.org/10.7860/JCDR/2021/47792.15092
Nandini Bhaduri Bhattacharyya, Anadi Roy Chowdhury, Susmita Mukhopadhyay, Sneha

1. Assistant Professor, Department of Pathology, RG Kar Medical College, Kolkata, West Bengal, India. 2. Professor, Department of Pathology, RG Kar Medical College, Kolkata, West Bengal, India. 3. Assistant Professor, Department of Pathology, RG Kar Medical College, Kolkata, West Bengal, India. 4. Junior Resident, Department of Pathology, RG Kar Medical College, Kolkata, West Bengal, India.

Correspondence Address :
Anadi Roy Chowdhury,
Kailash 502, Godrej Prakriti, 187f/1 BT Road, Sukhchar, West Bengal, India.
E-mail: dr-anadi@hotmail.com

Abstract

Introduction: Galectin-3 is a β-galactoside-binding lectin found in a considerable number of normal tissues and malignant neoplasms. It was found to be expressed in few thyroid tumours particularly follicular and papillary tumours. Lectins were found to be released in circulation and increased concentration was noted in colorectal cancers especially in metastatic colonic adenocarcinoma. Different types of galectins are expressed in normal colonic and rectal epithelium. Some types do increases in inflammation and cancers of these areas. It was seen that galectin-3 increases in colorectal tumourigenesis and it bears an important role in cancer progression and metastasis. Galectin-3 seems to have an important role in colorectal cancer. Some studies proved that galectin inhibitors could reduce tumour progression and metastasis and it may be a therapeutic target in metastatic colorectal adenocarcinoma.

Aim: To evaluate colon cancer specimens received for biopsy, for galectin-3 expression and its relation with tumour stage, lymphovascular space invasion and tumour differentiation.

Materials and Methods: The study was a cross-sectional observational study conducted in the Department of Pathology of RG Kar Medical College and Hospital from November 2018 to November 2019. It was an immunohistochemistry based assay performed to test the expression levels of galectin-3 in cancer tissues of 62 colorectal neoplasms with the help of galectin-3 primary antibody (mouse monoclonal antibody- clone 9C4). Statistical analysis was done using Statistical Package of Social Sciences (SPSS) version 19.0.

Results: Out of 62 cases, 60 cases were colorectal adenocarcinoma and 2 cases were adenoma with age group between 40-75 years. Total 46 cases had cancer in caecum and ascending colon and rest were in recto-sigmoid colon. A 36/60 cases (60%) of cancer tissues were positive for galectin-3 expression. Strong association of lymphovascular space invasion (p=0.046) and depth of tumour (p=0.0078) with galectin positivity in colon carcinoma was noted.

Conclusion: Evaluation of galectin-3 expression is helpful in the assessment of tumour staging and prognosis in colorectal cancer patients. It may have a therapeutic implication in the management of colon cancer in future.

Keywords

Colon cancer, Galactose binding, Immunohistochemistry, Lectin

Galectin-3 is an endogenous carbohydrate binding protein that is implicated in cell growth, differentiation, adhesion, malignant transformation and apoptosis. It is predominantly located in the cytoplasm. Galectin-3 seems to have an important role in colorectal cancer. Dabbs DJ examined the expression of galectin-1 and 3 in a series of few thyroid tumours and reported expression of these lectins in papillary and follicular carcinomas, but not in adenomas, nodular goitre, or normal thyroid tissue. Based on these studies, they concluded that the galectins could be useful in the distinction of benign and malignant thyroid tumours (1).

There is strong in-vitro and in-vivo evidence that tumourigenesis and metastasis can be reduced by galectin inhibitors. Galectin-3-null mice are relatively healthy, indicating that inhibition of galectin-3-mediated actions may present a viable and relatively safe therapeutic approach for cancer treatment (2).

Galectin-3 is also released into the circulation. Concentrations of circulating galectin-3 in the bloodstream of colorectal cancer patients can be increased up to five fold (3). Moreover, patients with metastasis have higher levels of circulating galectin-3 than those with localised tumours (4). The beta subunit of haptoglobin co-precipitates with galectin-3 from the serum of patients with colorectal cancer (4). Recent studies have suggested that the increased circulation of galectin-3 in the bloodstream of cancer patients can be an important promoter of cancer cell metastasis (5),(6).

In the normal human colon and rectum, four galectins, galectin(gal)-1, 3, 4 and 8, are expressed (7),(8),(9),(10). Galectin-1 is expressed weakly in normal colonic epithelium but its expression is increased in inflammation and cancer. The results on gal-1 and gal-3 clearly show that galectins are involved in the malignant progression of colon cancer and their migration properties (11).

Differential expression of galectin expression is very much common in cancers of the human gastrointestinal tract. Accumulating evidences support an active role of these endogenous carbohydrates binding protein in the regulation of colorectal cancer development, progression and distant metastasis (12).

Galectin-3 expression is greater in advanced cancer (13) and metastases express higher levels of galectin-3 than the primary tumours from which they arise (14). There is a general change in galectin-3 sub-cellular localisation from nucleus to the cytoplasm in colorectal cancer during progression from colorectal adenoma to carcinoma (8),(15). As cytoplasmic galectin-3 is known to be an apoptosis inhibitor, it is very likely that this change in localisation may contribute to cancer cell survival.

Galectin-4 is expressed in the human intestinal and colonic mucosa and its expression is generally lower in cancer than in normal mucosa (9),(16),(17).

Galectin-8 is expressed widely in the gastrointestinal tract. Low basal levels of galectin-8 are observed in the human intestine (18),(19). Hence, the present study aimed to evaluate the colon cancer specimens for galectin-3 expression and its relation with tumour stage, lymphovascular space invasion and tumour differentiation.

Material and Methods

The present study was an observational cross-sectional study carried out in the Department of Pathology, RG Kar Medical College, Kolkata, India from November 2018 to November 2019. Total 62 colorectal specimen with growth were collected during this period. Out of 62 cases, 40 cases were from male patients and 22 cases were from female patients. Institutional Ethics Committee permission (IEC No RKC/47) was taken.

Study Procedure

Surgically resected colorectal cancer tissues were fixed in 10% formalin and embedded in paraffin for routine pathological diagnosis. Paraffin blocks containing representative cancer tissue were selected and used for immunohistochemical study to see galectin 3 expression. The final result was achieved by multiplying the scores from the 2 categories: 0 to 3 points is negative expression; 4 to 6 points weakly positive expression (+), 7 to 9 points, fairly strong positive expression (++), 9 to 12 points, strong positive expression (+++) (13).

Tumour staging was done from assessment of depth of tumour penetration, lymphovascular invasion and lymph node metastasis. The IHC-2 sections of 2-3 μm thickness were prepared, one for H&E staining and one for IHC with galectin-3 primary antibody (mouse monoclonal antibody- clone number 9C4). The samples were evaluated by cell staining with the following scores: brown- 3 points; pale brown- 2 points; light brown- 1 point; and no colouration- 0 points. The quantity of stained cells was evaluated with the following scores: quantity of stained cells in one visual field of >75%- 4 points; 51% to 75%- 3 points; 11% to 50%- 2 points; less than 10%- 1 point, and negative- 0 points (13). (Table/Fig 1)a: Poorly differentiated colorectal carcinoma with Lymphovascular Space Invasion (LVSI) in surrounding area (100X magnification, H&E). (Table/Fig 1)b: Tumour deposit in the surrounding adipose tissue with LVSI. (100X magnification, H&E). (Table/Fig 1)c: strong positive galectin stain of 3×4=12 score (IHC) and (Table/Fig 1)d: weakly positive galectin stain of 2×2=4 score (IHC) in this study.

Statistical Analysis

Statistical analysis was done using 2×2 contingency table from each category with the help of SPSS version 19.0 and Chi-square test was done to assess level of significance.

Results

In this study the expression of galectin-3 in 62 tissue specimens were assessed, which included 2 adenomas (one rectal villous adenoma and one was traditional serrated adenoma in ascending colon) and 60 cases of colon carcinomas of known Tumour Node Metastasis (TNM) stage. Therefore, the result analysis was done on 60 cases only, excluding the adenomas. The average age of 62 patients in this study was between 40 years to 75 years. There were 40 males and 22 females. A total of 46 cases had tumour in ascending colon and caecum and 16 had tumour in recto-sigmoid region. Total 36 out of 60 (60%) of the tumours showed galectin-3 expression. The various parameters studied for galectin-3 expression are: 1) Tumour stage; 2) LVSI; and 3) Tumour differentiation.

Clinicopathologic characteristics of all the cases are shown in (Table/Fig 2). There is strong association (p-value <0.05) of Lymphovascular space invasion and galectin positivity in colon carcinoma which is depicted in (Table/Fig 3). Strong association was also noted in cases of depth of tumour and galectin positivity (p-value=0.014 i.e., p<0.05) noted in (Table/Fig 4).

There was also increased negativity of galectin in relation to tumour differentiation in colorectal carcinoma shown in (Table/Fig 5). Poorly differentiated carcinoma show 13/19 (68.4%) negative expression compared to well differentiated carcinoma where only 5 out of 13 cases (38.4%) showed negative expression.

Discussion

Galectin-3 is an endogenous carbohydrate binding protein implicated in cell growth, differentiation, adhesion, malignant transformation and apoptosis. Being predominantly located in the cytoplasm, it seems to have an important role in colorectal carcinogenesis.

In the present study, patients were in stage 2 in 17 cases and in stage 3 and stage 4 combined in 43 cases. 6 cases of stage 2 tumour, were galectin-3 positive and 30 cases in stages 3 and 4 were galectin-3 positive. The p-value was 0.014 and significant (p<0.05).

A total of 39 samples were LVSI positive and 27 of them were galectin-3 positive. Twenty one cases were negative for LVSI. Out of LVSI negative cases 9 were galectin-3 positive. The p-value was calculated to be 0.046, result is significant at p<0.05.

Similar study was done by Schoeppner HL et al., on galectin-3 expression in 153 tissue specimens. They found galectin-3 expression was significantly higher in high grade dysplasia and early invasive cancers compared with the adenomatous tissue. A linear relationship noted between galectin-3 expression in invasive cancers with advancing stage (p=0.008). Decreased long term patient survival (p=0.021) correlated with enhanced expression. Higher level of galectin-3 expression noted in metastasis compared with the primary cancers (p<0.005) (14).

A similar study using immunohistochemistry assay was used to test the expression status of galectin-3 in cancer tissues of 61 colorectal cancer (61 cases) and in normal intestinal mucosa adjacent to the cancer (23 cases). Clinicopathological features, such as age, sex, pathological type, lymphatic metastasis, and prognosis were also analysed with the galectin-3 level. Rate of positivity of galectin-3 in cancer tissues was significantly higher than that of normal epithelium adjacent to cancer 62.5% (38/61) versus 13.0% (3/23) (p<0.05) respectively. Positive correlation was noted between the protein expression of galectin-3 and the tumour size (p<0.05), tumour differentiation (p<0.05) and dukes stage (p<0.05) (20).

Another similar study conducted in Kyushu University, Fukuoka, Japan on 121 colorectal cancer patients, showed positive expression in 65% patients. The incidence of lymph node metastasis was significantly high in galectin-3 positive cases with significance level p<0.05 (p=0.0007). Deeper invasion into wall and lymphatic permeation was higher in positive cases (p=0.01 and p=0.041, respectively). Larger tumour size had higher expression (p=0.016) (21).

Another study conducted in Department of General Surgical Science of Gunma University Graduate School of Medicine, Maebashi, Japan on 108 patients with colorectal cancer was investigated using immunohistochemical analysis. Galectin-3 expression at the surface of the tumour was correlated with the depth of invasion (p=0.02) and blood vessel invasion (p<0.01) in this study (22).

A study from a chinese article showed that galectin 3 was expressed in 158 cases including 30 normal mucosa, 25 adenomas, 65 carcinomas and 38 metastatic tumour specimens. Normal tissues showed different expression than adenomas (p<0.001). Poorly differentiated and colorectal cancer with metastasis showed higher expression than well and moderately differentiated tumours (p=0.03 and p<0.001, respectively). Invasive tumours had higher expression than non invasive tumours (p<0.001) (23).

Limitation(s)

Not all parameters were satisfactorily described in the present study because of low sample size. It can be made more statistically significant if a large sample size would be taken.

Conclusion

Immunohistochemical detection of elevated expression of galectin-3 is a potent prognostic marker in colorectal cancer, but its biological function is still to be explored. Elucidation of this function may contribute to our search for a new therapeutic regime against cancer progression and metastasis in future. The higher expression of galectin-3 may contribute as a metastasis predictor for colorectal carcinoma. This study is restricted in this regard due to low sample volume. Further studies are needed.

Acknowledgement

Authors would like to thank Prof. (Dr.) Tushar Kanti Das, Head of the Department, Department of Pathology, and all technical staff of the department.

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DOI and Others

10.7860/JCDR/2021/47792.15092

Date of Submission: Nov 15, 2020
Date of Peer Review: Dec 31, 2020
Date of Acceptance: Feb 17, 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? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Nov 17, 2020
• Manual Googling: Feb 13, 2021
• iThenticate Software: Mar 15, 2021 (19%)

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