Immunohistochemical study of glutathione S-transferase in preneoplastic and neoplastic lesions of human urinary bladder

Moon, Woo Chul; Kim, In Kyu; Kim, Young Sun; Park, Yong Wook; Song, Kae Yong

Abstract

Glutathione S-transferase(GST) is a family of enzymes which plays an important role in cellular detoxification by catalyzing the conjugation of electrophilic xenobiotics with glutathione and recently have been shown to be closely associated with chemical carcinogenesis and resistance to cytotoxic drugs in several types of malienancies. However, it remains ill-defined about the role of GST in bladder tumor. Herein we performed immunohistochemical study using polyclonal antibody directed against acidic(pi form) and basic GST and analyzed the intensity(0-3+) and proportion(grade 1-4) of staining in bladder specimens from 50 patients with bladder tumor and from 10 normal controls. On GST-pi immunohistochemical stain, normal bladder mucosa was stained only focally and in low intensity, whereas the staining intensity and proportion were significantly increased in transitional cell hyperplasia, dysplasia /carcinoma in situ(CIS), and overt carcinoma (p<0.05). The staining intensity and proportion of GST-pi were significantly lower in invasive and high grade (III, IV/VI) transitional cell carcinoma(TCC) compared to superficial and low grade TCC (p<0.001). There were no significant differences in the intensity and proportion of GST-pi staining between superficial bladder TCC which recurred and which did not recur after prophylactic intravesical chemotherapy. On basic GST immunohistochemical stain, normal bladder as well as preneoplastic and neoplastic lesions or the bladder showed only focal and low intensity staining. These results suggest that GST-pi may be a marker of preneoplatic lesions and low grade, superficial TCC or bladder and that invasive and high grade TCC of bladder may have another cellular deloxilication mechanism different from GST. GST may not be the major mechanism of drug resistance in superficial bladder TCC. The role or basic GST in normal bladder as well as in bladder TCC is in doubt.