Histochemical and Immunohistochemical Assessment of Bladder Cancer and it is Association with Urinary Schistosomiasis among Sudanese Patients

Abstract

This is a descriptive retrospective study carried out in Khartoum state-Sudan during the period between November 2008 to May 2011.The study aimed at histological and immunohistochemical assessment of the bladder cancers and its association with urinary schistosomiasis among Sudanese patients. Samples from 194 patients were included (87 with SCC, 68 with TCC and 39 with benign bladder cystitis). Their ages ranging from 34 to 91years with the mean ages of 58.06 for SCC, 69.49, 75.26 for TCC and cystitis respectively. The male female ratio was 1.6:1. The great majority of patients were from Central Sudan constituting 101 of whom 49 bladder SCCs, 31 TCCs and 21 with bladder cystitis. For each specimen 4 histopathological procedures were performed; AgNORs (histochemical), ki67, COX2 and iNOS (immunohistochemical). COX2 and iNOS were significantly higher in SCC and TCC compared to cystitis group (p.value = 0.000), 82/87 (94.3%) of bladder SCC were stained positive for COX2, and 39/68(57.4%) of TCC similarly stained positive, while 18/39(46.2%) of bladder cystitis expressed COX2 but all with low intensity. 74/87(85.1%) of SCC stained positive for iNOS; the marker was expressed among 22/68 (32.2%) of TCC, and for cystitis group only 17/39(43.6%) were positive but all with low intensity (P. value was 0.000). Significant increase in mean of cells stained positive for the COX2 and iNOS markers from cystitis group to TCC to SCC was observed (p.value = 0.000) With regard to COX2 and iNOS immunoreactivity in schistosomal and non schistosomal associated bladder pathology; significant effect of schistosomal ova presence to both markers was observed as all schistosomiasis associated SCC (28 out of 28) samples were immunopositive for COX2, five out of 59 of non schistosomal associated SCCs were negative for COX2. Nine out of ten of schistosomal associated TCC expressed COX2, compared to 30 out of 58 non schistosomal TCC positive for the marker. Ten out of 12 of schistosomal associated cystitis were positive for COX2 while only eight out of 27 of non schistosomal cystitis were positive for COX2 marker. iNOS was expressed in all schistosomal associated SCCs but only in 46 out of 59 of non schistosomal type. For TCC; six out of ten of schistosomal type was positive compared to only 14 out of 58 of non schistosomal samples. Similar effect was observed in cystitis group; all schistosomal type has expressed the marker but only seven out of 29 of non schistosomal were positive for iNOS. COX2 and iNOS markers were co expressed in 83.9% of SCC, 22.1% TCC and in 28.2% of cystitis samples. Significant decline in means of AgNORs dots from SCC to TCC to bladder cystitis was observed, the study revealed significant difference between means of AgNORs among different bladder pathology (mean difference between SCC and TCC was 1.001, p.value = 0.000), between SCC and cystitis mean difference was 2.224, p.value = 0.000) and between TCC and cystitis was 1.223, p.value = 0.001). The means of AgNORs dots increase from cystitis to TCC to SCC samples. Significant difference in Ki67 proliferative marker expression was observed between bladder tumors and cystitis group; 155/155 (100%) of bladder tumors were positive with different intensity compared to 31/39(79.5%) of benign bladder cystitis were stained positive and all cystitis samples stained with low intensity. The role of AgNORs and ki-67 in differentiating between schistosomal related bladder tumor and non schistosomal related bladder tumor is still controversial. Both COX2 and iNOS biomarkers are strongly associated with urinary schistosomal bladder cancer; therefore it might be useful as indicators and discriminatory markers for bladder cancer in general and schistosomal associated one in particular.On the basis of these findings it is concluded that; all four investigated indicators play significant roles in bladder carcinogenesis, therefore we recommend the consideration of these procedures in the assessment of individuals at risk.