High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients

• Type: Article in International Scientific Journal
• Date: 2007

Authors

henrique, rmf (Author) ICBAS; Ribeiro, FR (Author) Other; Fonseca, D (Author) Other; Hoque, MO (Author) Other; Carvalho, AL (Author) Other; Costa, VL (Author) Other; Pinto, M (Author) Other; Oliveira, J (Author) Other; Manuel R Teixeira (Author) ICBAS; Sidransky, D (Author) Other; Carmen Jeronimo (Author) ICBAS

Journal

Title: Clinical Cancer Research

Vol. 13

Pages: 6122-6129

ISSN: 1078-0432

Publisher: American Association for Cancer Research

Indexing

ISI Web of Knowledge - 93 Citations

Scopus - 102 Citations

Other information

Authenticus ID: P-004-6SK

DOI: 10.1158/1078-0432.ccr-07-1042

Abstract (EN): Purpose: Prostate cancer is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. Owing to the limitations of current clinical, serologic, and pathologic parameters in predicting disease progression, we sought to investigate the prognostic value of promoter methylation of a small panel of genes by quantitative methylation-specific PCR (QMSP) in prostate biopsies. Experimental Design: Promoter methylation levels of APC, CCND2, GSTP1, RARB2, and RASSF1A were determined by QMSP in a prospective series of 83 prostate cancer patients submitted to sextant biopsy. Clinicopathologic data [age, serum prostate-specific antigen (PSA), stage, and Gleason score] and time to progression and/or death from prostate cancer were correlated with methylation findings. Log-rank test and Cox regression model were used to identify which epigenetic markers were independent predictors of prognosis. Results: At a median follow-up time of 45 months, 15 (18%) patients died from prostate cancer, and 37 (45%) patients had recurrent disease. In univariate analysis, stage and hype rmethylation of APC were significantly associated with worse disease -specific survival, whereas stage, Gleason score, high diagnostic serum PSA levels, and hypermethylation of APC, GSTP1, and RASSF1A were significantly associated with poor disease-free survival. However, in the final multivariate analysis, only clinical stage and high methylation of APC were significantly and independently associated with unfavorable prognosis, i.e., decreased disease-free and disease-specific survival. Conclusions: High-level APC promoter methylation is an independent predictor of poor prognosis in prostate biopsy samples and might provide relevant prognostic information for patient management.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8