BIOMARKER STUDY OF PRIMARY NONMETASTATIC VERSUS METASTATIC INVASIVE BLADDER-CANCER

A cohort of 109 patients with primary transitional cell carcinomas, st ages T-2-T-3, grade 2 or higher, was identified and further divided in to two groups based on lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of detectable metastatic disease over a mini mum of 5 years of follow-up after cystectomy (n = 52). Blocks correspo nding to the primary tumor lesions were sectioned and distributed to d ifferent laboratories to be analyzed, Immunohistochemistry on deparaff inized tissue sections was conducted for evaluation of p53 nuclear ove rexpression (monoclonal antibody PAb1801), assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and microvascular cou nts (factor VIII-related antigen). DNA content/ploidy studies were per formed on material obtained from thick sections. A double-blinded stra tegy was used for the evaluation of laboratory data versus clinical pa rameters. The cutoff value for p53 nuclear overexpression was greater than or equal to 20% of tumor cells displaying nuclear staining. The m edian values for MIB1 (greater than or equal to 18% of tumor nuclear c ell staining) and microvascular counts (greater than or equal to 40 mi crovessels/area screened) were used as cutoff points for these two var iables. The assessment of DNA content was conducted by classifying cas es as diploid, tetraploid, or aneuploid, Statistical analyses were per formed using the Fisher's Exact Test (2-tailed). Results revealed that none of the markers studied had a statistically significant correlati on with the end point of the study, i.e., the presence of lymph node m etastatic disease, in the cohort of patients studied, although an obvi ous trend for p53 was noted, It is concluded that alterations of p53, Ki-67 proliferative index, microvascular counts, and ploidy are not st rongly associated with lymph node status in patients affected with hig h-stage, high-grade bladder cancer.