Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma.
OBJECTIVE
In this study, we tested the ability of a panel of hypermethylation markers to improve the sensitivity of histologic prostate cancer detection in sextant needle biopsies.


METHODS
We obtained fresh-frozen sextant biopsies from 72 excised prostates and directly compared blinded histologic review and quantitative real-time methylation-specific PCR for hypermethylation of four genes, Tazarotene-induced gene 1 (TIG1), adenomatous polyposis coli (APC), retinoic acid receptor beta2 (RARbeta2), and glutathione S-transferase pi (GSTP1) to detect the presence of prostate cancer. Results were compared with the final surgical pathological review of the resected prostates as the gold standard.


RESULTS
Histologic review alone detected carcinoma with a sensitivity of 64% (39 of 61 cases) and 100% specificity. Quantitative real-time methylation-specific PCR for TIG1, APC, RARbeta2, and GSTP1 detected carcinoma with a sensitivity of 70%, 79%, 89%, and 75%, respectively, with 100% specificity for all of the genes. Using this panel of methylation markers in combination with histology resulted in the detection of 59 of 61 (97%) cases of prostate with 100% specificity, a 33% improvement over histology alone.


CONCLUSIONS
The use of a panel of methylation markers as an adjunct to histologic review may substantially augment prostate cancer diagnosis from needle biopsies.
Tokumaru
Yutaka
Y
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Harden
Susan V
SV
Sun
Dong-Il
DI
Yamashita
Keishi
K
Epstein
Jonathan I
JI
Sidransky
David
D
D000217:Acyltransferases / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics; D019175:DNA Methylation; D017491:Genes, APC; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics
D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D000217:Acyltransferases; C043403:fatty acyl ethyl ester synthase