AN IMMUNOHISTOCHEMICAL AND PROGNOSTIC EVALUATION OF CATHEPSIN-D EXPRESSION IN 105 BLADDER CARCINOMAS

Cathepsin D is a widely expressed aspartyl lysosomal protease. Clinica l studies in several tumor types have shown a strong correlation betwe en cathepsin D expression and tumor progression. In breast carcinoma, its expression is an independent prognostic factor associated with an increased risk of death. However, there have been no studies evaluatin g cathepsin D in bladder tumors. Therefore, the aim of this study was to determine the pattern of expression of cathepsin D in a large serie s of bladder carcinomas and assess its role as a prognostic factor aga inst established variables. The tumors from 105 patients (median age 7 3) (median follow-up 26 months) with transitional cell carcinoma of bl adder were examined. Forty-nine patients had superficial tumors (16 pT a; 33 pT1), 56 had invasive tumors (14 pT2; 42 pT3); there were 35 gra de 1/2 tumors and 70 grade 3 tumors. These were stained by a standard immunohistochemical technique with an anti-cathepsin D monoclonal anti body. All 4 normal bladder specimens were positive for cathepsin D. Fi fty-four tumors (51%) were positive for cathepsin D and 51 (49%) were negative. Chi square analysis showed a significant positive relationsh ip between negative cathepsin D expression and stage (p <0.0005), grad e (p <0.0001) and tumor morphology (p 0.001). There was no relationshi p between cathepsin D expression and tumor ploidy (p >0.1) or patient age (p = 0.09). Univariate analysis of disease-free and overall surviv al showed that negative cathepsin D expression (p = 0.01 and p = 0.000 3 respectively), stage (p = 0.004 and p <0.005 respectively) and grade (p = 0.02 and p = 0.0007 respectively) were associated with significa ntly worse prognosis. However, in a multivariate analysis of age, stag e, grade and cathepsin D expression, only stage remained significant f or overall survival (p <0.005). The observed result for cathepsin D in the univariate analysis is probably due to its strong association wit h grade and stage. Nevertheless, cathepsin D status was able to provid e additional prognostic information for overall survival in invasive t umors when stratifying for grade (p = 0.047), which suggests that it m ight provide additional prognostic data within particular tumor stages .