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CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2018; 39(02): 172-177
DOI: 10.4103/ijmpo.ijmpo_81_17
Original Article

Study of Clinicopathological Spectrum and Pattern of Expression of Cyclooxygenase‑2 in Urothelial Carcinomas of Bladder

Ranjana Bandyopadhyay
Department of Pathology, Calcutta National Medical College, Kolkata, West Bengal, India
,
Ujjwal Bandyopadhyay
Department of Pathology, Calcutta National Medical College, Kolkata, West Bengal, India
,
Uttara Chatterjee
Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
,
Sukla Naskar
Department of Pathology, Calcutta National Medical College, Kolkata, West Bengal, India
,
Sumit Nandy
Department of Pathology, Calcutta National Medical College, Kolkata, West Bengal, India
,
Keya Basu
Department of Pathology, Calcutta National Medical College, Kolkata, West Bengal, India
› Author Affiliations Financial support and sponsorship Nil.
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Abstract

Introduction: Overexpression of cyclooxygenase-2 (COX2) in urothelial carcinoma of bladder (UCB) had been studied in the past by different workers and the results were contradictory. The objective of the present study was to evaluate the prognostic implication of COX2 expression in primary urothelial carcinomas of the urinary bladder and its correlation with clinical parameters, tumor stage, grade, and recurrence. Materials and methods: A total of 68 cases who underwent surgery for urothelial carcinoma in our medical college from January 2013 to December 2015 were evaluated in our study. Hematoxylin and eosin-stained slides were examined by two faculties applying standard reporting protocol. Tumor staging and grading was performed as per the WHO guidelines. Immunohistochemistry for expression of COX2 was performed to study any correlation of tumor grade with COX2 expression. The distribution of COX2 positivity was studied in tumors stratified according to established bladder cancer prognostic factor, for example, tumor size, grade, invasion, and spread. Results: Out of 68 cases, 42 cases showed COX2 positivity (61%). In low-grade cases of bladder carcinoma, COX2 positivity was 16 out of 24 cases (60%), and in high-grade cases, COX2 positivity was 10 out of 18 cases (64.28%).Conclusion: In the present study, the association of COX2 overexpression with advanced tumor invasion and tumor grade has been substantiated. Hence, COX2 expression can be taken as a prognostic factor along with other usual prognostic factors in patients of UCB.

Keywords

Cyclooxygenase-2 expression - urothelial carcinoma - tumor grade


Publication History

Article published online:
23 June 2021

© 2018. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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  • References

  • 1 May M, Bastian PJ, Brookman-May S, Fritsche HM, Tilki D, Otto W. et al. Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a. Urol Oncol 2013; 31: 1141-7
    CrossrefPubMedGoogle Scholar
  • 2 Bruins HM, Arends TJ, Pelkman M, Hulsbergen-van de KaaCA, van der HeijdenAG, Witjes JA. et al. Radical cystectomy in a Dutch University hospital: Long-term outcomes and prognostic factors in a homogeneous surgery-only series. Clin Genitourin Cancer 2014; 12: 190-5
    CrossrefPubMedGoogle Scholar
  • 3 Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol 2009; 27: 289-93
    CrossrefPubMedGoogle Scholar
  • 4 Latif Z, Watters AD, Dunn I, Grigor KM, Underwood MA, Bartlett JM. HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder. Br J Cancer 2003; 89: 1305-9
    CrossrefPubMedGoogle Scholar
  • 5 Otto W, May M, Fritsche HM, Dragun D, Aziz A, Gierth M. et al. Analysis of sex differences in cancer-specific survival and perioperative mortality following radical cystectomy: Results of a large German multicenter study of nearly 2500 patients with urothelial carcinoma of the bladder. Gend Med 2012; 9: 481-9
    CrossrefPubMedGoogle Scholar
  • 6 May M, Stief C, Brookman-May S, Otto W, Gilfrich C, Roigas J. et al. Gender-dependent cancer-specific survival following radical cystectomy. World J Urol 2012; 30: 707-13
    CrossrefPubMedGoogle Scholar
  • 7 Botteman MF, Pashos CL, Redaelli A, Laskin B, Hauser R. The health economics of bladder cancer: A comprehensive review of the published literature. Pharmacoeconomics 2003; 21: 1315-30
    CrossrefPubMedGoogle Scholar
  • 8 Hong SK, Kwak S, Jeon HG, Lee E, Lee SE. Do vascular, lymphatic, and perineural invasion have prognostic implications for bladder cancer after radical cystectomy?. Urology 2005; 65: 697-702
    CrossrefPubMedGoogle Scholar
  • 9 Zigeuner R, Shariat SF, Margulis V, Karakiewicz PI, Roscigno M, Weizer A. et al. Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract. Eur Urol 2010; 57: 575-81
    CrossrefPubMedGoogle Scholar
  • 10 Xylinas E, Rink M, Robinson BD, Lotan Y, Babjuk M, Brisuda A. et al. Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer 2013; 49: 1889-97
    CrossrefPubMedGoogle Scholar
  • 11 Mitra AP, Bartsch CC, Bartsch GJr, Miranda G, Skinner EC, Daneshmand S. Does presence of squamous and glandular differentiation in urothelial carcinoma of the bladder at cystectomy portend poor prognosis? An intensive case-control analysis. Urol Oncol 2014; 32: 117-27
    CrossrefPubMedGoogle Scholar
  • 12 Wheeler MA, Hausladen DA, Yoon JH, Weiss RM. Prostaglandin E2 production and cyclooxygenase-2 induction in human urinary tract infections and bladder cancer. J Urol 2002; 168(4 Pt 1): 1568-73
    CrossrefPubMedGoogle Scholar
  • 13 Shirahama T. Cyclooxygenase-2 expression is up-regulated in transitional cell carcinoma and its preneoplastic lesions in the human urinary bladder. Clin Cancer Res 2000; 6: 2424-30
    PubMedGoogle Scholar
  • 14 Diamantopoulou K, Lazaris A, Mylona E, Zervas A, Stravodimos K, Nikolaou I. et al. Cyclooxygenase-2 protein expression in relation to apoptotic potential and its prognostic significance in bladder urothelial carcinoma. Anticancer Res 2005; 25: 4543-9
    Google Scholar
  • 15 Eltze E, Wülfing C, Von StruenseeD, Piechota H, Buerger H, Hertle H. Cox-2 and Her2/neu co-expression in invasive bladder cancer. Int J Oncol 2005; 26: 1525-31
    PubMedGoogle Scholar
  • 16 Friedrich MG, Toma MI, Petri S, Huland H. Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence. BJU Int 2003; 92: 389-92
    CrossrefPubMedGoogle Scholar
  • 17 Gudjónsson S, Bendahl PO, Chebil G, Höglund M, Lindgren D, Lundberg LM. et al. Can tissue microarray-based analysis of protein expression predict recurrence of stage Ta bladder cancer?. Scand J Urol Nephrol 2011; 45: 270-7
    CrossrefPubMedGoogle Scholar
  • 18 Hilmy M, Campbell R, Bartlett JM, McNicol AM, Underwood MA, McMillan DC. The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration and COX-2 expression and survival in patients with transitional cell carcinoma of the urinary bladder. Br J Cancer 2006; 95: 1234-8
    CrossrefPubMedGoogle Scholar
  • 19 Czachorowski MJ, Amaral AF, Montes-Moreno S, Lloreta J, Carrato A, Tardón A. et al. Cyclooxygenase-2 expression in bladder cancer and patient prognosis: Results from a large clinical cohort and meta-analysis. PLoS One 2012; 7: e45025
    CrossrefPubMedGoogle Scholar
  • 20 Hsu FS, Hsin C, Tu PY, Pu SY. The role of cyclooxygenese-2 expression in chemoresistance and invasiveness of urothelial carcinoma. Imp J Interdiscip Res 2016; 2: 979-86
    Google Scholar
  • 21 Fajkovic H, Halpern JA, Cha EK, Bahadori A, Chromecki TF, Karakiewicz PI. et al. Impact of gender on bladder cancer incidence, staging, and prognosis. World J Urol 2011; 29: 457-63
    CrossrefPubMedGoogle Scholar
  • 22 Cao D, Vollmer RT, Luly J, Jain S, Roytman TM, Ferris CW. et al. Comparison of 2004 and 1973 World Health Organization grading systems and their relationship to pathologic staging for predicting long-term prognosis in patients with urothelial carcinoma. Urology 2010; 76: 593-9
    CrossrefPubMedGoogle Scholar
  • 23 Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou-Redorta J. et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol 2011; 59: 997-1008
    CrossrefPubMedGoogle Scholar
  • 24 Stein JP, Quek ML, Skinner DG. Lymphadenectomy for invasive bladder cancer: I. historical perspective and contemporary rationale. BJU Int 2006; 97: 227-31
    CrossrefPubMedGoogle Scholar
  • 25 Lotan Y, Gupta A, Shariat SF, Palapattu GS, Vazina A, Karakiewicz PI. et al. Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol 2005; 23: 6533-9
    CrossrefPubMedGoogle Scholar
  • 26 Hara S, Miyake H, Fujisawa M, Okada H, Arakawa S, Kamidono S. et al. Prognostic variables in patients who have undergone radical cystectomy for transitional cell carcinoma of the bladder. Jpn J Clin Oncol 2001; 31: 399-402
    CrossrefPubMedGoogle Scholar
  • 27 Leissner J, Koeppen C, Wolf HK. Prognostic significance of vascular and perineural invasion in urothelial bladder cancer treated with radical cystectomy. J Urol 2003; 169: 955-60
    CrossrefPubMedGoogle Scholar
  • 28 Yoshimura R, Sano H, Mitsuhashi M, Kohno M, Chargui J, Wada S. Expression of cyclooxygenase-2 in patients with bladder carcinoma. J Urol 2001; 165: 1468-72
    CrossrefPubMedGoogle Scholar
  • 29 Wild PJ, Kunz-Schughart LA, Stoehr R, Burger M, Blaszyk H, Simon R. et al. High-throughput tissue microarray analysis of COX2 expression in urinary bladder cancer. Int J Oncol 2005; 27: 385-91
    PubMedGoogle Scholar
  • 30 Wülfing C, Eltze E, von Struensee D, Wülfing P, Hertle L, Piechota H. Cyclooxygenase-2 expression in bladder cancer: Correlation with poor outcome after chemotherapy. Eur Urol 2004; 45: 46-52
    CrossrefPubMedGoogle Scholar
  • 31 Margulis V, Shariat SF, Ashfaq R, Thompson M, Sagalowsky AI, Hsieh JT. Expression of cyclooxygenase-2 in normal urothelium, and superficial and advanced transitional cell carcinoma of bladder. J Urol 2007; 177: 1163-8
    CrossrefPubMedGoogle Scholar
  • 32 Shirahama T, Arima J, Akiba S, Sakakura C. Relation between cyclooxygenase-2 expression and tumor invasiveness and patient survival in transitional cell carcinoma of the urinary bladder. Cancer 2001; 92: 188-93
    CrossrefPubMedGoogle Scholar
  • 33 Ferrandina G, Lauriola L, Zannoni GF, Distefano MG, Legge F, Salutari V. et al. Expression of cyclooxygenase-2 (COX-2) in tumour and stroma compartments in cervical cancer: Clinical implications. Br J Cancer 2002; 87: 1145-52
    CrossrefPubMedGoogle Scholar
  • 34 Matsuo T, Miyata Y, Mipsunari K. Pathological significance and prognostic implications of heme oxygenese1 expression in non muscle invasive bladder cancer: Correlation with cell proliferation, angiogenesis, lymphangiogenesis and expression of VEGFs and cox2. Oncol Lett 2017; 13: 275-80
    CrossrefPubMedGoogle Scholar
  • 35 Prabhu B, Balakrishnan D, Sundaresan S. Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats. Hum Exp Toxicol 2016; 35: 685-92
    CrossrefPubMedGoogle Scholar