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

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On Sep 2018

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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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On Aug 2018

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"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".

Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
On Aug 2018

Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".

Dr. Mamta Gupta
(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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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)
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.
On April 2011

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
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : December | Volume : 16 | Issue : 12 | Page : EC34 - EC37 Full Version

Significance of Ki67, BCL 2 Immunoexpression in Urothelial Carcinoma and their Association with Grading and Staging: A Descriptive Cross-sectional Study

Published: December 1, 2022 | DOI:
Prithwish Ray, Sanjayay Sarkar, Seema Mondal, Anadi Roy Chowdhury

1. Senior Resident, Department of Pathology, Asansol District Hospital, Asansol, West Bengal, India. 2. Assistant Professor, Department of General Medicine, Nil Ratan Sirkar Medical College and Hospital, Kolkata, West Bengal, India. 3. Associate Professor, Department of Pathology, Diamond Harbour Government Medical College and Hospital, Kolkata, West Bengal, India. 4. Professor, Department of Pathology, Murshidabad Medical College and Hospital, Kolkata, West Bengal, India.

Correspondence Address :
Seema Mondal,
84/A, Kalianibasmain Road, [Barrackpore], P.S. Titagrh, District- North 24 Pargana, Kolkata-700122, West Bengal, India.


Introduction: Urinary bladder is the most common site of malignancy in the urinary tract and the most common type of cancer of urothelial origin is urothelial cell carcinoma. This subtype constitutes more than 90% of bladder cancer. Histological grade of tumour is one of the most important predictive parameter for prognosis and biological behavior of urothelial carcinoma. As some crucial discordances may arise between pathologists because of subjectivity, so immunohistochemistry can be used for accurate diagnosis and prediction of prognosis.

Aim: To study the immununohistochemical expression of B-Cell Lymphoma 2 (BCL 2) and Ki (Kiel)-67 markers and their association with tumour grade and stage in urothelial carcinomas.

Materials and Methods: A descriptive cross-sectional study was conducted in the Department of Pathology of a tertiary care R G Kar Medical College and Hospital, Kolkata, West Bengal, India. West Bengal, India, on a total of 75 cases from January 2018 to June 2019. The study population comprised of cases of urothelial lesions as diagnosed by cystoscopy, who underwent standardised operative procedures. Relevant sections were taken from different parts of the fixed specimens. Histopathological Examination (HPE) was done to confirm the presence or absence of non-invasive and invasive carcinoma, and the depth of invasive tumour cells for pathological staging. Evaluation of the level of cytological and architectural disorder at low and medium magnification (100X and 200X) were done for grading. Cytological disorder were defined as abnormalities in nuclear size, shape, and chromatin, while architectural disorder were defined as abnormalities in the orientation of the cells in relation to each other and to the basement membrane of the papillae. Immunohistochemical analysis was done for Ki67 and BCL 2 expression in paraffin embedded sections in all the cases. In this study, chi-square test was done with International Business Management(IBM) Statistical Package for Social Sciences (SPSS), as per which, the association between two variables is statistically significant if p value is <0.05.

Results: Out of total 75 cases (mean age: 67.3 years) analysed, 58 cases (77.3%) had Invasive type of bladder neoplasm, followed by low grade papillary urothelial carcinoma 10 (13.3%), and papillary urothelial neoplasm of low malignant potential 07 (9.3%). Ki67 expression in urothelial carcinoma has more significance because 59 cases (78.7%) showed high level expression (>20%) out of 75 cases, whereas only 12 (16%) cases show high level expression (4+) of BCL 2 marker.

Conclusion: Ki67 overexpression is seen more commonly, than BCL 2, in high grade tumours as well as in advanced stage. So Ki67 may be used as a marker to predict aggressive behavior and to differentiate low grade and high grade tumours also.


B-cell lymphoma 2, Immunohistochemistry, Kiel-67 gene, Muscle invasion, Urinary bladder

Bladder cancer was the 10th most commonly diagnosed malignancy worldwide, accounting for 549,393 new cases and 199,922 deaths in 2018 (1),(2). Urothelial cell carcinoma is the predominant histologic subtype of bladder cancer, contributing to more than 90% of bladder cancer cases (3). On microscopic examination, the detection of the invasion of the tumour process to sub epithelial tissues is important to determine its effect on therapeutic measures as well as prognosis of the disease process (2),(3).

The invasion of urothelial carcinoma to sub epithelial tissues proceeds in two stages: invasion of the lamina propria and invasion of the muscle layer. The detection of the former is difficult and that of the latter has great significance because of its influence on therapy and prognosis, both regarding recurrence as well as survival. Tumours that invade the deep muscle layer of bladder are assigned stage T2, while T3 and T4 lesions invade the perivesicle tissue and local structures respectively (1),(2),(3),(4),(5).

Stage of malignancy is an important determinant for a patient’s outcome in most solid organ malignancies (4),(5),(6) Overall, the five-year survival drops to 38.5% for stage T2 as compared to 70% in stage T0 and T1 bladder cancer patients. However, histological grade is considered an equally, or even more, important prognostic factor in particular for the superficial urothelial neoplasms of the bladder, a category that includes tumours either with only lamina propria invasion or without invasion. It has been demonstrated that grade strongly correlates with recurrence and the presence of, or progression to muscle invasive disease (muscularispropria invasion) in superficial urothelial neoplasms (7).

This study discusses the current understanding of emerging biomarkers Ki 67 and BCL 2 and their potential clinical value in Bladder Cancer (BC) diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practices. Ki67 is a non-histone nuclear protein with a short life. It is strictly associated with cell proliferation, which is present during all active phases of the cell cycle (G1, S, G2, and mitosis). Ki67 is a preferably convenient biomarker for the proliferation status of tumour cells (8),(9),(10). Recently, several studies continuously reported that Ki67 is an independent indicator to predict poor clinical outcomes of both no muscle invasive and muscle invasive BC patients. Apoptosis (programmed cell death) and the genes regulating this process (e.g., BCL 2) have recently become a focus of interest in the study of cancer development and progression.

The BCL 2 gene product plays a role as an inhibitor of apoptosis; it contributes to oncogenesis by suppressing signals that induce apoptotic cell death (11),(12). BCL 2 is a protein that helps control whether a cell lives or dies by blocking a type of cell death called apoptosis (13).

Therefore, the present study was conducted with the aim to compare and determine the association of Ki67 and BCL 2 immunoexpression in urothelial carcinoma as well as their significance in grading and staging.

Material and Methods

This descriptive cross-sectional study was conducted in the Department of Pathology, in collaboration with Department of Urosurgery, at R G Kar Medical College and Hospital, Kolkata, from January 2018 to June 2019 after approval from the Institutional Ethical Committee (RKC/Ethics/30).

Inclusion criteria: Those patients who presented clinically with symptoms suspicious of urothelial carcinomas like painless, gross haematuria, nocturia, dysuria or urgency of micturition and were radiologically diagnostic of urothelial neoplasms of urinary bladder. For histopathological confirmation, specimens of both Transurethral Resection of Bladder Tumour (TURBT) as well as radical cystectomy were examined.

Exclusion criteria: Those cases with mesenchymal tumours (angioma, myoma, fibroma, sarcoma etc.) arising from the bladder, primary adenocarcinomas arising from urachal remnant or areas of glandular metaplasia, pure squamous cell neoplasms, all inflammatory (inflammatory pseudopolyps, interstitial cystitis etc.) conditions in bladder, and all cases of bladder lithiasis were excluded from the study.

Total of 75 cases were included in the study following the inclusion and exclusion criteria.

Study Procedure

The medical history, radiological, and other investigation reports were checked. Cystectomy specimen or TURP chips of bladder was obtained from the Urosurgery Department in which site of tumour was also mentioned. All tissues were examined grossly and microscopically for appropriate pathological stage evaluation. The tumours were categorised as Ta (non-invasive urothelial carcinoma), Tis (urothelial carcinoma in situ), T1 (tumour involving lamina propria), T2 disease (tumour involving muscularispropria), T3 (Tumour invades perivesical soft tissue) or T4 (extravesical tumour directly invading any of the following: prostatic stroma, seminal vesicles, uterus,vagina, pelvic wall, abdominal wall).Nodal dissection specimens were received in separate packets and all lymph nodes examined microscopically, as both the number and the location of positive lymph nodes are important to asses prognosis (14).

Histopathological findings with grading is reported, grading of tumour was based on the evaluation of the level of cytological and architectural disorder microscopically (15). Immunohistochemical (IHC) staining for Ki67 and BCL 2 were also done. Then association of Ki67 and BCL 2 with clinicopathological parameters were studied.

Poly-L-Lysine coated slides were prepared as follows: Poly-L-Lysine [Sigma chemicals] was dissolved in distilled water (i.e., 1:10 dilution) and then dried. Preparation of Tris (Trisaminomethane)- Ethylene Diamine Tetra-acetic Acid (EDTA) Buffer (Antigen-Retrieval buffer) was done.

Preparation of TRIS Buffer (Wash buffer) and % Hydrogen peroxide: 9.6 gm of TRIS (Molecular weight (Mol. wt.): 121.14) add 8.7 gms of Sodium chloride (NaCl) (MERCK, no: 7647-14-5) were dissolved in 1000 mL of distilled water. 97 mL of distilled water, 3 mL of H2O2 was added to make 3% of H2O2. Primary antibody was used according to the immunohistochemical markers. Preparation of 3,3- Diaminobenzidine (DAB) solution was done. Then following procedure is done for staining:

• Removal of Paraffin and Rehydration
• Antigen Retrieval-Unmasking of Antigen
• Inactivation of Endogenous Peroxidase with 3% hydrogen
Primary Antibody Reaction in which the primary antibody was diluted to its optimal dilution in diluent. The diluent alone was used as a negative control. Than a positive control slide was also run.
• Secondary Antibody Reaction in which secondary antibody was diluted in the diluent to its optimal dilution.
• Counterstaining with Mayer’s haematoxylin.

Ki67 scoring system and criteria: Cells stained for Ki67 were counted and expressed as a percentage. The percentage was determined by the number of Ki67 positive cells among the total number of counted tumour cells (at least 1000) with nuclear staining in each case. High expression of Ki67 was defined as ≥20% and low level expression was defined as less than 20% immunoexpression (16).

BCL 2 scoring system and criteria: Only cytoplasmic staining was scored as positive for BCL 2, regardless of the intensity of the stained cells. BCL 2 expression (17) was assessed as follows:

1. Negative (0)-No immunoreactivity detectable.
2. Weakly positive (1+) when less than 5% of the cells show positive for BCL 2.
3. Moderate positive (2+) 5 to 50% of tumour cells are positive.
4. Strong positive (3+) more than 50% of tumour cells are positive.

For positive controls of BCL 2 and Ki67 follicular lymphoma and normal tonsil were stained respectively.

Statistical Analysis

The statistical analyses were performed using the SPSS version 23.0 software program. Relationships among the clinicopathological factors and BCL 2, Ki67, expressions were analysed using chi-square test and Fisher exact t-test. The results were considered statistically significant if the p-value was ≤0.05.


The present study was done on total 75 cases who were admitted to the inpatient Department of Urosurgery, for bladder tumour and they underwent surgery. Mean age was 67.3 years (range was 42 to 86), (Table/Fig 1). A total of 59 cases were above the age of 65 years and 16 cases were below this age. Gender distribution showed that most of the cases were male (72%) with a male to female ratio is 18:7. According to site of origin, most of the tumours were located in right and left lateral wall and posterior wall of bladder, together they comprises most of the common sites of origin of tumour (Table/Fig 2).

Distribution of different histologic variants were-invasive (77.3%), low grade and papillary urothelial neoplasm of low malignant potential. (Table/Fig 3) Gross examination (Table/Fig 4)a,b of specimens was done. Low-grade lesions (Table/Fig 4)c,d have long, delicate papillae with minimal branching and fusing. At low magnification, they have a relatively orderly appearance, but at medium magnification mild pleomorphism and some loss of polarity is found. But in high grade carcinoma (Table/Fig 4)e,f the papillae may be fused, cellular disorder, nuclear size variation and irregular and pleomorphic nuclei are readily apparent at low to intermediate magnification.

Irregular prominent nucleoli and numerous mitoses, including irregular forms are typical. In (Table/Fig 5), high-level Ki67 (Table/Fig 5)a expression in nuclei of tumour cells and low level BCL 2 (Table/Fig 5)b cytoplasmic expression is shown. Total 24 cases of low grade carcinoma were studied and 15 cases showed high level Ki67 immunoexpression but only three cases showed high level immunoexpresion of BCL 2. There were 51 cases of high grade carcinoma, out of which 44 cases showed high level immunoexpression of Ki67 whereas only 9 cases showed high level immunoexpression of BCL 2.

Association of Ki67 expression with clinicopathological parameters were summarised in (Table/Fig 6). The Ki67 expression was more in advance cases. Association between stage of tumour with both Ki67 and BCL 2 expression was also studied. The p-value is greater than 0.05 (0.6430) in BCL 2 expression, so there is no association between BCL 2 expressions and staging of urothelial carcinoma cases. Association between histological grade of urothelial tumour and BCL 2 expression was also evaluated. It was concluded that since the p value is greater than 0.05, there is no association between BCL 2 expressions and grading of urothelial carcinoma cases. Whereas association between histopathological grade of bladder tumour and Ki67 expression was also studied. Analysis of data suggested an association between Ki67 expressions with grading (p-value 0.019) of urothelial carcinoma cases. High grade carcinoma cases showed very high expression.


In this study, association of clinicopathological features with molecular marker Ki67 and BCL 2 expression was evaluated systematically in different type of bladder cancer. It has been found that low level Ki67 is commonly seen in low grade bladder carcinoma and high Ki67 expression was associated with the more aggressive clinical stage and larger size tumour in bladder cancer patients. Ki67 expression was not strongly associated with age, gender, and tumour site in these patients. Some researchers investigated the relationships between the Ki67 and distant metastases (18). In this study of 75 cases, it has been found that Ki67 expression was elevated with advanced age and with the progression of tumour grade (p-value=0.0190). The largest series to date, reported by Jeon HG et al., (19) on 107 Upper urinary Tract Urothelial Carcinoma (UTUC) patients, revealed that Ki67 overexpression was an independent risk factor.

A number of studies have examined the role of BCL 2 as a prognostic factor of bladder cancer outcome. Most studies did not identify a prognostic significance of this marker (19),(20). Nakopoulou L et al., found that a loss of BCL 2 positivity had an unfavorable prognosis; however, in multivariate analysis, there was no independent prognostic value (20). In contrast, Lipponen PK et al., (21) reported that a heterogeneous group of tumours with BCL 2-positive non-basal cells had an unfavorable prognosis but in multivariate analysis, expression of BCL 2 had no independent prognostic value. In a study by Kong G et al., all find the BCL 2 positive rate was much lower than that reported previously (7% to 69%) and was not related to tumour grade or pathological stage (22).

Nakopoulou L et al., found a strong positive correlation of mitotic indices and Ki67 with tumour grade (20), Ki67 ≥59% and mitotic count ≥36.50 per 10 High Power Field (HPF), if proven seem to be promising and reliable indicators to assess muscle invasion in superficial bladder biopsies and TURBT samples where muscle is not resected. Epstein JI et al.found recurrence and tumour progression the expression of Ki67 was significantly higher in high grade tumours (14). Tony T et al., opined that combined use of p53 and Ki67 immunomarkers in urinary bladder carcinomas may provide additional prognostic information along with histological grading and staging (23).

Ogata DC et al., found high grade Transitional Cell Cancer (TCC) had a higher frequency of positivity for this antibody (24). Matsumoto H et al., found comparing pathological stage and histological grade, histological grade correlated with increasing stage and Ki67 expressions in bladder UCs increased with pathological stage and histological grade and that it was possible to obtain more accurate information about the biological behavior of UC by evaluating these parameters together with morphological findings (25).

Stanton MJ et al., and Wang L et al., also found Ki67 labelling index as an independent predictor of tumour, recurrence for patients with primary superficial low grade bladder cancers. They concluded that determination of tumour growth kinetics by Ki67 index antibody might help to identify more biologically aggressive tumours and help physicians select patients with superficial bladder cancer who require more intense follow-up and/or prophylactic intravesical chemotherapy instillation (26),(27).


The study sample was limited. This study needs to be extrapolated to a large population-based sample with financial support sufficient enough to find relationship of expression of biomarker with grade and stage of tumour and findings need to be confirmed by a larger prospective cohort study.


In conclusion, tumour stage and grade is not associated with BCL 2 but there was a strong similarity with Ki67 proliferation index. This study confirmed the significant associations between Ki67 expression with some clinicopathological features (advanced age) and histological grade in bladder carcinoma, so Ki67 immunoexpression may be helpful to identify patients at high risk who may benefit by adjuvant therapies.


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DOI and Others

DOI: 10.7860/JCDR/2022/56653.17354

Date of Submission: Mar 26, 2022
Date of Peer Review: May 09, 2022
Date of Acceptance: Oct 29, 2022
Date of Publishing: Dec 01, 2022

• 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. NA

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