Cyclooxygenase‐2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinoma

Abstract

Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins. It contributes to human carcinogenesis by various mechanisms. The aim of the current study was to elucidate the possible involvement of COX-2 in human bladder carcinoma by examining its expression on both urothelial and inflammatory cells in tissue biopsies and urine cytology samples of different urinary bladder lesions. A total of 65 patients were included in the study and were selected from cases admitted to Urology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. They represented seven control cases with almost normal-looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma (SqCC) (n=10). Immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections and urine cytology samples was performed for all cases using COX-2 (H-62): sc-7951, a rabbit polyclonal antibody. The study revealed positive COX-2 expression on the urothelial and inflammatory cells of cystoscopic biopsies from all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with 42.8% and 71.4% of normal controls, respectively. The score of urothelial COX-2 expression was sequentially up-regulated from normal to chronic cystitis (either pure or associated with premalignant changes) (p<0.05) to malignant changes (p<0.05). However, the inflammatory cellular expression was down-regulated with malignant transformation compared with chronic cystitis (p<0.05). In TCC, COX-2 was over-expressed on both urothelial and inflammatory cells in advanced tumors. Urine cytology samples were positive for COX-2 in a comparable manner to that observed in cystoscopic biopsies. Accordingly, the results of the current study have provided new information in two aspects: First, is the possibility of using the differential COX-2 expression on both inflammatory and urothelial cells as markers for premalignant or malignant transformation; second, besides cystoscopy, urine cytology was found to have a high sensitivity for COX-2 expression and hence proved to be valuable in malignancy as a non-invasive substitute for cystoscopy.

Immunohistochemical expression of COX2 and iNOS in bladder cancer and its association with urinary schistosomiasis among Sudanese patients

“…The development of squamous cell carcinoma is closely correlate with chronic urinary tract infection; therefore, COX-2 plays an important role in inflammation-induced carcinogenesis. These findings agree with some studies [20,21] in this context. These studies found that COX-2 is expressed in squamous cell carcinomas of the urinary bladder and in the precursor lesions.…”

The role of cyclooxygenase-2 in ulcerative colitis and colorectal adenocarcinoma

“…Patients with ulcerative colitis are at increased risk for developing CRC as inflammation may help cancer cell precursors become fully malignant (Moussa et al, 2009). Thus, prevention of inflammation, which aids cancer development, can be achieved.…”

COX2/mPGES1/PGE 2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells

“…This fact may suggest that PD-L1 can be induced in tumor vicinity via interaction with tumor-recruited inflammatory cells frequently presented in cancer tissues. Bladder cancer, in particularly, is characterized by the marked infiltration with immune and inflammatory cells such as macrophages and myeloid-derived suppressor cells (MDSCs) of bone marrow (BM) origin (6)(7)(8)(9). Peripheral blood in cancer patients, including those with bladder cancer, also comprises high numbers of myeloid cells, indirectly indicating that tumors may recruit BM-derived cells to support tumor growth through multiple mechanisms including local immunosuppression in tumor site (10,11).…”