title: Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer. National Cancer Institute Bladder Tumor Marker Network.
abstract: A cohort of 109 patients with primary transitional cell carcinomas, stages T2-T3, grade 2 or higher, was identified and further divided into two groups based on lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of detectable metastatic disease over a minimum of 5 years of follow-up after cystectomy (n = 52). Blocks corresponding to the primary tumor lesions were sectioned and distributed to different laboratories to be analyzed. Immunohistochemistry on deparaffinized tissue sections was conducted for evaluation of p53 nuclear overexpression (monoclonal antibody PAb1801), assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and microvascular counts (factor VIII-related antigen). DNA content/ploidy studies were performed on material obtained from thick sections. A double-blinded strategy was used for the evaluation of laboratory data versus clinical parameters. The cutoff value for p53 nuclear overexpression was > or =20% of tumor cells displaying nuclear staining. The median values for MIB1 (> or =18% of tumor nuclear cell staining) and microvascular counts (> or =40 microvessels/area screened) were used as cutoff points for these two variables. The assessment of DNA content was conducted by classifying cases as diploid, tetraploid, or aneuploid. Statistical analyses were performed using the Fisher's Exact Test (2-tailed). Results revealed that none of the markers studied had a statistically significant correlation with the end point of the study, i.e., the presence of lymph node metastatic disease, in the cohort of patients studied, although an obvious trend for p53 was noted. It is concluded that alterations of p53, Ki-67 proliferative index, microvascular counts, and ploidy are not strongly associated with lymph node status in patients affected with high-stage, high-grade bladder cancer.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: P
authors.initials: P
authors.lastname: Lianes
authors.forename: E
authors.initials: E
authors.lastname: Charytonowicz
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Y
authors.initials: Y
authors.lastname: Fradet
authors.forename: H B
authors.initials: HB
authors.lastname: Grossman
authors.forename: G P
authors.initials: GP
authors.lastname: Hemstreet
authors.forename: F M
authors.initials: FM
authors.lastname: Waldman
authors.forename: K
authors.initials: K
authors.lastname: Chew
authors.forename: L L
authors.initials: LL
authors.lastname: Wheeless
authors.forename: D
authors.initials: D
authors.lastname: Faraggi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology / Q000556:secondary*; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000032:analysis; D004311:Double-Blind Method; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D014841:von Willebrand Factor