title: An immunohistochemical and prognostic evaluation of cathepsin D expression in 105 bladder carcinomas.
abstract: Cathepsin D is a widely expressed aspartyl lysosomal protease. Clinical studies in several tumor types have shown a strong correlation between 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 evaluating cathepsin D in bladder tumors. Therefore, the aim of this study was to determine the pattern of expression of cathepsin D in a large series of bladder carcinomas and assess its role as a prognostic factor against established variables. The tumors from 105 patients (median age 73) (median follow-up 26 months) with transitional cell carcinoma of bladder were examined. Forty-nine patients had superficial tumors (16 pTa; 33 pT1), 56 had invasive tumors (14 pT2; 42 pT3); there were 35 grade 1/2 tumors and 70 grade 3 tumors. These were stained by a standard immunohistochemical technique with an anti-cathepsin D monoclonal antibody. All 4 normal bladder specimens were positive for cathepsin D. Fifty-four tumors (51%) were positive for cathepsin D and 51 (49%) were negative. Chi square analysis showed a significant positive relationship between negative cathepsin D expression and stage (p < 0.0005), grade (p < 0.0001) and tumor morphology (p = 0.001). There was no relationship between cathepsin D expression and tumor ploidy (p > 0.1) or patient age (p = 0.09). Univariate analysis of disease-free and overall survival showed that negative cathepsin D expression (p = 0.01 and p = 0.0003 respectively), stage (p = 0.004 and p < 0.005 respectively) and grade (p = 0.02 and p = 0.0007 respectively) were associated with significantly worse prognosis. However, in a multivariate analysis of age, stage, grade and cathepsin D expression, only stage remained significant for overall survival (p < 0.005). The observed result for cathepsin D in the univariate analysis is probably due to its strong association with grade and stage. Nevertheless, cathepsin D status was able to provide additional prognostic information for overall survival in invasive tumors when stratifying for grade (p = 0.047), which suggests that it might provide additional prognostic data within particular tumor stages.
authors.affiliation: Department of Urology, Bristol Royal Infirmary, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Dickinson
authors.forename: S B
authors.initials: SB
authors.lastname: Fox
authors.forename: P V
authors.initials: PV
authors.lastname: Newcomb
authors.forename: R A
authors.initials: RA
authors.lastname: Persad
authors.forename: G N
authors.initials: GN
authors.lastname: Sibley
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis / Q000235:genetics*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D002402:Cathepsin D