Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer Journal Article


Authors: Lianes, P.; Charytonowicz, E.; Cordon-Cardo, C.; Fradet, Y.; Grossman, H. B.; Hemstreet, G. P.; Waldman, F. M.; Chew, K.; Wheeless, L. L.; Faraggi, D.; National Cancer Institute Bladder Tumor Marker Network
Article Title: Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer
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 ≤20% of tumor cells displaying nuclear staining. The median values for MIB1 (≤18% of tumor nuclear cell staining) and microvascular counts (≤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.
Keywords: immunohistochemistry; human tissue; major clinical study; cancer staging; lymphatic metastasis; ki-67 antigen; biological marker; metastasis; cohort studies; tumor markers, biological; bladder cancer; protein p53; tumor marker; urinary bladder neoplasms; cancer invasion; dna; dna, neoplasm; tumor suppressor protein p53; neoplasm invasiveness; carcinoma, transitional cell; double-blind method; transitional cell carcinoma; dna content; ploidy; von willebrand factor; humans; human; priority journal; article; monoclonal antibody ki 67
Journal Title: Clinical Cancer Research
Volume: 4
Issue: 5
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 1998-05-01
Start Page: 1267
End Page: 1271
Language: English
PUBMED: 9607586
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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  1. Pilar Llanes
    11 Lianes