Immunohistochemical Demonstration of C-erbB-2 Oncoprotein Expression in Transitional Cell Carcinoma of the Bladder: Correlative Study with Tumor Grade, Stage, Proliferating Cell Nuclear Antigen Expression, Nucleolar Organizer Regions Per Nucleus, and Flow

Yoo, Ji; Cheon, Jun; Kim, Han Kyeum; Kim, Je Jong; Koh, Sung Kun

Abstract

C-erbB-2 oncoprotein has been known to act as growth factor receptor responsible for the regulation of cellular growth, proliferation and differentiation and has been demonstrated in a number of cancers by immunohistochemical as well as matrix blotting techniques. Breast and ovarian cancer patients, whose tumor cells have amplification or overexpression of this oncoprotein, have been suggested to have worse prognosis. Yet, there are only a few studies on c-erbB-2 oncoprotein expression in transitional cell carcinoma(TCC) of the bladder. The aim of this study was to examine c-erbB-2 oncoprotein expression in bladder cancer to assess its potential as a useful prognostic marker in transitional cell carcinoma of the bladder. Deparaffinized tumor specimens from 42 patients with TCC of the bladder and 3 normal bladder tissue specimens were utilized. C-erbB-2 oncoprotein expression was detected by immunohistochemical analysis and then correlated with conventional prognostic variables such as histologic tumor grade, stage and DNA ploidy. In addition, we related the expression of c-erbB-2 oncoprotein to indicators of cellular proliferative activities such as proliferating cell nuclear antigen(PCNA), mean number of silver nucleolar organizer regions(AgNORs) per nucleus, flow cytometric S-phase fraction(CPF) and proliferation index(PI). The incidence of c-erbB-2 oncoprotein expression in Ash grade IV TCC of bladder was higher than that in Ash grade II and III (Chi-square test, p<0.05). The incidence of positive immunoreaction was higher in cases with muscle invasion and metastasis than in superficial tumors with statistical significance(p<0.05). In addition, statistical significant correlation was noted between c-erbB-2 oncoprotein expression and PCNA expression rate. But there were no significant differences in c-erbB-2 oncoprotein expression to DNA ploidy, PI nor SPF by flow cytometry and mean number of AgNORs per nucleus. The results of this study suggests that the c-erbB-2 oncoprotein together with other predictive parameters may serve to provide a phenotypic profile which permits more accurate forecasting of bladder cancer behavior and may prove to be useful in the future as an important guide to specific anti-tumor therapy.