Hypermethylation of the CpG islands in the promoter region of the GSTP1 gene in prostate cancer: a useful diagnostic and prognostic marker?
BACKGROUND
Recently, many studies have focused on the potential diagnostic value of the promoter hypermethylation of the GSTP1 gene in prostate cancer.


METHODS
A total of 144 patients, undergoing eight-core prostatic biopsies for a clinically suspected prostate cancer, was analyzed. Two different tissue samples were collected from the same area of the prostate and then divided for both genomic DNA extraction and pathological examination. In order to perform molecular analysis, prostatic tissue samples were digested with the methylation-sensitive restriction enzyme HpaII and then amplified by conventional polymerase chain reaction (PCR).


RESULTS
Prostate cancer was diagnosed in 42/144 patients, and promoter hypermethylation of GSTP1 gene was detected in 31/42 of prostate cancer (sensitivity=74%) and in 2/102 of negative specimens (specificity=98%). A significant association between GSTP1 promoter hypermethylation both with a Gleason score >or=7 (Fisher's exact P=0.01) and the presence of Gleason grade 4 and/or grade 5 (Fisher's exact P=0.03) was found.


CONCLUSIONS
Promoter hypermethylation of the GSTP1 gene is a highly specific--but not a very sensitive--marker of prostate cancer. Our data showed a significant association between the methylation status of the GSTP1 gene and Gleason score and grade, suggesting a potential prognostic value of this epigenetic DNA alteration.
Bernardini
Sergio
S
Department of Internal Medicine, Policlinico Tor Vergata, University of Tor Vergata, Rome, Italy. Bernardini@Med.UniRoma2.it
Miano
Roberto
R
Iori
Roberta
R
Finazzi-Agrò
Enrico
E
Palmieri
Giampiero
G
Ballerini
Sabrina
S
Angeloni
Caterina
C
Orlandi
Augusto
A
Bellincampi
Lorenza
L
Cortese
Claudio
C
Federici
Giorgio
G
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics
D014408:Biomarkers, Tumor; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase