Development of an Assay for Prostate Cancer Based on Methylation Status of Glutathione S-Transferase (p).

摘要

Glutathiaone-s-transferase (GST)-Pi gene is frequently methylated in prostate cancer and recent evidence has linked aberrant expression of this gene with the development of prostatic adenocarcinomas (PACs). The main purpose of this study is to evaluate GST-Pi protein expression by immunohistochemistry (IHC) and develop a simple DNA amplification assay for detection of GST-Pi methylation status. 220 cases including 180 PACs and 20 cases each of normal and benign hyperplastic tissues were identified. Protein expression was evaluated on 4 micrometers paraffin sections in all cases using a polyclonal rabbit antihuman GST-Pi antibody by an automated method. Methylation status was assessed in 176 cases including 155 PACs and 21 benign tissues using 466/468 and 425/430 primer pairs by a gel based PCR amplification method. 175 of 180 (97%) PACs demonstrated loss of GST-Pi protein expression in comparison to the presence of this protein in 100% of benign tissues including normal and BPH specimens. 127 of 155 (82%) cases of PACs and 1 of 21 (5%) benign tissues demonstrated methylated GST-Pi promoter DNA. Given that the overwhelming majority of PACs lacked GST-Pi protein expression, no correlation was found with any prognostic variables. In conclusion, GST-Pi protein is downregulated in almost all prostate cancers and is associated with methylation of the promoter region of the gene. Further studies are warranted to evaluate the utility of GST-Pi methylation assay in screening and diagnosis of prostate cancer.