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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
Expression of ERG in Prostatic Acinar Adenocarcinoma Diagnosed on TRUS-guided Biopsy and its Association with WHO Grade Group- A Prospective Observational Study
Correspondence Address :
SM Sarfaraj,
SSKM PGT Hostel, 242, Harish Mukherjee Road, Kolkata-700020, West Bengal, India.
E-mail: drsmsarfaraj@gmail.com
Introduction: Prostate cancer is a common malignancy affecting men and the second leading cause of cancer related death in India. Numerous molecular biomarkers have been evaluated for their potential role in predicting disease progression, their response to therapy and survival. Erythroblast Transformation Specific (ETS) related Gene (ERG) is one of the newest addition in the existing list of biomarkers of prostate cancer.
Aim: To analyse the expression of ERG in prostatic adenocarcinoma and to evaluate its association with World Health Organisation (WHO) grade group.
Materials and Methods: This was a prospective observational study was conducted in the Department of Pathology in association with Department of Urology, IPGME&R, SSKM Hospital, Kolkata, West Bengal, India. The duration of the study was 1.5 years, from January 2019 to June 2020. A total of 267 cases of Transrectal Ultrasound (TRUS) guided tru-cut biopsy was included. Clinical data including preoperative Prostate Specific Antigen (PSA) level, Digital Rectal Examination (DRE) were obtained. Histopathological reports were prepared by two pathologists along with Gleason scoring and WHO grading as per 2014 International Society of Urological Pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma. Formalin Fixed Paraffin Embedded (FFPE) sections of representative blocks of each tumour was selected for Immunohistochemistry (IHC) study. Only the cases which had more than 10% nuclear staining were considered as positive. Statistical analysis was performed with help of Epi Info (TM) 7.2.2.2 and Chi-square test was used to test the association of different study variables.
Results: The mean age of the study participants was 65.55 years, and the age range was 45-93 years. Among the 80 malignant cases where, ERG immunostaining was assessed, 28 cases (35%) showed positive expression. Among these positive cases, 50% cases were weakly positive, 28.57% showed moderate positivity and 21.43% had strong positive expression. Highest positivity was observed in WHO grade group V (44.83%). The intensity of ERG expression was also higher in high grade group (13) than low grade group cancer patients.
Conclusion: ERG expression in the prostate cancer can be a prognostic factor as the expression and intensity of expression both increases with higher grade group of cancer.
Carcinoma prostate, Erythroblast transformation specific related gene, Immunohistochemistry, Transrectal ultrasound, World health organisation
Prostate cancer is the 8th most common cause of cancer death overall, and the 5th most common cause of cancer death worldwide for males (1). The Indian scenario also follows the global trend with prostate being the second leading site of cancer among males in cities like Delhi and Kolkata. There is dispute regarding the use of serum levels of PSA as a tool of public health screening for prostate cancer. Definitive diagnosis is primarily based on core needle biopsy which is usually prompted by suspicious clinical presentation such as Lower Urinary Tract Symptoms (LUTS), elevated serum PSA level, suspicious DRE, and TRUS or Magnetic Renosance Imaging (MRI) findings (2). Numerous molecular biomarkers have been evaluated for their potential role in predicting disease progression, response to therapy, and survival in prostate cancer patients (3). These efforts have been greatly facilitated by the wealth of information garnered from gene expression array studies and by sophisticated bioinformatics tools evaluating the overwhelming data sets generated from genomic, transcriptomic, and proteomic studies. Genomic technologies are yielding new markers that can in turn be evaluated for clinical use in a high throughput manner using Immunohistochemistry (IHC) and Fluorescence In Situ Hybridisation (FISH) labelled tissue microarrays and state-of-the-art image analysis systems (4).
Transmembrane Serine Protease 2 (TMPRSS2)-ERG fusion is a frequent event in prostate cancer. PSA screened hospital based cohort studies detect a frequency of TMPRSS2-ERG fusion, ranging between 40% and 78% (5). ERG IHC may offer an accurate, simpler, and less costly alternative for evaluation of ERG fusion status in prostate cancer on needle biopsy and radical prostatectomy samples (6),(7),(8). In the present study, the expression of ERG oncoprotein expression in prostatic carcinoma using immunohistochemical staining was analysed and a relationship between ERG positivity and intensity with World Health Organisation (WHO) grade group was also assessed.
A prospective observational study was conducted in the Department of Pathology in association with Department of Urology at a tertiary care Hospital, Kolkata, West Bengal, India. The duration of the study was 1.5 years, from January 2019 to June 2020. The study was carried out in accordance with the ethical principles stated by the declaration of Helsinki principles and was approved by the Institutional Ethical Committee (IPGME&R/IEC/2019/004).
Inclusion criteria: Relevant patient particulars had been obtained along with history and documentation from bed head tickets. Thus, by feasibility method of non randomised sampling, 267 cases fulfilling the above mentioned inclusion criteria were included in the study.
Exclusion criteria: On sectioning and further processing, 29 cases with tiny TRUS cores did not yield sufficient tumour tissue for ERG interpretation and the patients refusing to give consent and insufficient biopsy samples on IHC study were excluded from the study.
Study Procedure
Whenever TRUS guided biopsy of a suspected case of prostatic carcinoma with high serum PSA level (>4 ng/mL) and prostatomegaly on (DRE had been received from Department of Urology, the particular patient was approached in the urology ward for necessary consent. All those samples underwent histopathological examination and out of total selected cases, 109 cases were diagnosed as prostatic adenocarcinomas. These biopsy proven prostatic adenocarcinoma cases were subjected for ERG immunostaining. Hence, interpretation of ERG expression was done on 80 biopsy proven prostatic adenocarcinoma cases. ERG expression status was compared with WHO grade group of prostatic adenocarcinoma as proposed by 2014 ISUP Consensus Conference on Gleason Grading of Prostatic Carcinoma (9). The parameters examined during histopathological assessment were- tumour load, presence of prostatic intraepithelial lesion, presence of perineural invasion, Gleason score and WHO grade group (Table/Fig 1). The slides were examined under the light microscopy (olympus magnus 2 CX20i). The reporting was done by two experienced pathologists. There was interobserver variability in one prostatic carcinoma case, which was interpreted by one pathologist as benign with severe prostatitis (kappa value=0.992763). Later, IHC staining for PSA and Tumour Protein 63 (P63) was done on that specimen and both pathologists agreed that, to be a prostatic carcinoma. Gleason scoring and WHO grade were calculated as per 2014 ISUP consensus conference on Gleason grading of prostatic carcinoma (9).
Interpretation of IHC
For immunohistochemical evaluation FFPE sections of representative blocks of each tumour was selected. The authors used anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) for ERG.
Only the cases which had more than 10% positive nuclear staining for ERG were considered as positive (10).
The intensity of ERG positivity was scored as (11):
• No staining (0)
• Weak staining (1+)
• Moderate staining (2+)
• Intense staining (3+)
Endothelial cells were considered as positive control (Table/Fig 2).
Statistical Analysis
Statistical analysis was performed with help of Epi Info (TM) 7.2.2.2 Epi info is a trademark of the Centre for Disease Control and prevention (CDC). Using this software, basic cross-tabulation, inferences and associations were performed. Chi-square test was used to test the association of different study variables. Z-test (Standard Normal Deviate) was used to test the significant difference between two proportions. The p <0.05 was considered to be statistically significant.
The mean age of the study participants undergoing TRUS-guided biopsy were 65.55 years, and the age range was 45-93 years. Out of total 267 TRUS-guided biopsy cases, 148 cases (55.43%) were benign, whereas, 109 cases were diagnosed as acinar adenocarcinoma (40.82%). Among other categories 5 cases were diagnosed as Atypical Small Acinar Proliferation (ASAP) (1.87%), 3 cases were diagnosed as High Grade Prostatic Intraepithelial Neoplasia (HGPIN) (1.13%), and biopsy was found to be inadequate in 2 cases (0.75%) (Table/Fig 3).
The prevalence of malignant cases was significantly higher among the patients with age between 65-74 years. The authors also found 49 malignant cases (44.95%) in that age range. Out of 80 prostatic adenocarcinoma cases, 6 cases were in Gleason grade group II (7.5%); 9 cases were in grade group II (11.25%); 12 cases were in grade group III (15%); 24 cases were in grade group IV (30%) and 29 cases were in grade group V (36.25%). Average tumour load was 56±4.567%. Associated HGPIN was identified in 10 cases (12.5%). Evidence of perineural invasion was identified in 55 cases out of 80 cases (68.7%). Most of the malignant cases 77 out of 80 cases, (96.25%) had the PSA level more than 4 ng/mL. Hence, PSA had high sensitivity in diagnosis of malignancy. The distribution of malignant cases according to the WHO grade group and PSA levels were not statistically significant (p-value=0.291) (Table/Fig 4).
ERG immunoreactivity and gleason grade: The ERG status was estimated in total 80 biopsy proven prostatic adenocarcinoma patients. A total of 28 cases (35%) were positive while 52 cases (65%) were negative. Among these positive cases, 50% cases were weakly positive, 28.57% showed moderate positivity and 21.43% had strong positive expression. The relationship between Gleason grade and ERG IHC is summarised in (Table/Fig 3). ERG expression was detected in higher primary Gleason grade than in the lower grade (p-value=0.005). Highest positivity was in WHO grade group V (44.83%) (Table/Fig 5).
Additionally, the strong intensity of ERG expression were mostly found in grade group V (66.7%) (Table/Fig 6). The lower grade group (grade group I and II) prostatic adenocarcinomas were mainly negative for ERG immunostaining or weakly/moderately positive.
Recurrent genetic fusion of TMPRSS2 and ERG in prostate cancer was first reported by Pettersson A et al., (12). ERG (ETS-related gene) is an oncogene located on chromosome 21 (21q22.2). The ERG gene encodes for a protein, also called ERG, which functions as a transcriptional regulator. The most common TMPRSS fusions is with ERG, resulting in the TMPRSS2-ERG fusion, which has been identified in approximately 23% to 50% of prostate cancer cases in different cohorts (13). The fusion gene is critical to the progression of cancer because, it prevents the androgen receptor expression and it binds and inhibits androgen receptors already present in the cells. Essentially TMPRSS2-ERG fusion disrupts the ability of the cells to differentiate into proper prostate cells creating unregulated and unorganised tissue (14).
Since, early days after the discovery of the TMPRSS2-ERG fusion gene, many groups have searched for its clinical implications on the prognosis of prostatic acinar adenocarcinoma. However, variability in study population, clinical profiles and the methods for gene fusion detection has led to divergent expression results. In a study by Barwick BG et al., TMPRSS2-ERG fusion was associated with the disease recurrence in multiple cohorts (15). However, Hermans KG et al., found that, the TMPRSS2-ERG gene fusion is significantly related to a favorable prognosis (16). Several articles showed TMPRSS2-ERG gene fusion expression as an independent predictor of poor outcome in prostate carcinoma (17),(18). However, other studies have indicated that, the ERG gene fusion has no significant clinical implications or prognostic value (19),(20).
In the present study, ERG positivity rate was 35%, which is relatively higher than other prostate cancer based studies. In Japanese population study by Furusato B et al., and Miyagi Y et al., a relatively lower rate of ERG positivity has been reported (20.1% and 28%) [21,22]. Study by Hashmi AA et al., showed ERG protein expression in 39.7% cancer cases (31 cases out of 78 cases), which is near to the present study (11). Among the positive cases of prostatic adenocarcinomas in the present study, 50% cases were weakly positive, 28.57% showed moderate positivity and 21.43% had strong positive expression. Association between TMPRSS2-ERG fusion gene status and clinicopathological profile remained variable in multiple studies. Some studies showed that, lower Gleason score and grade group is associated with highest expression of ERG fusion gene (23),(24). Few groups however, found no significant association between Gleason score and ERG expression (25),(26). Newer studies like Mannan R et al., revealed higher expression of ERG gene fusion with higher Gleason scores and grades (10). In the present study, ERG expression was detected in higher primary Gleason grade than in the lower grade (p-value=0.005). Highest positivity was in WHO grade group V (44.83%) which is in concordance with recent studies.
In the present study, intensity of ERG expression in prostatic adenocarcinoma was also more in higher WHO grade groups. The high Gleason scores like 9/10 or grade group V had the highest intensity of ERG IHC expression (4 out of 6 strong positive ERG, 66.7%). A study by Hashmi AA et al., showed similar findings (11). Although, IHC is a suitable surrogate for fluorescent insitu hybridisation/polymerase chain reaction based detection of ERG, it can not specify the mutation/fusion type or the fusion partner (27).
Limitation(s)
The present study was limited in the aspect of shorter sample size and limited duration in a single Institution-based study samples.
The present study recommends that, the ERG expression is a prognostic marker of prostatic adenocarcinoma and its expression predicts the higher grade in prostate carcinoma patients. Whenever present, strong intensity of ERG expression is also associated with high histological grades of prostatic adenocarcinoma.
DOI: 10.7860/JCDR/2023/61485.17815
Date of Submission: Nov 16, 2022
Date of Peer Review: Jan 11, 2023
Date of Acceptance: Feb 28, 2023
Date of Publishing: May 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
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