PTENmutation, methylation and expression in breast cancer patients.
The tumor suppressor gene,PTEN, has previously been demonstrated to be involved in breast tumorigenesis and tumor progression. The aim of the present study was to investigate the expression and significance ofPTENin breast carcinomas, to detect the mutation frequency ofPTENin sporadic breast carcinoma tissues and to determine the association betweenPTENpromoter methylation and gene expression. Immunohistochemical methods were used to analyze the expression of thePTENgene in 146 cases of breast carcinoma and 10 cases of normal breast tissue closely adjacent to the carcinoma. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis was used to analyze conformation polymorphisms in 45 breast carcinoma and 10 normal breast tissues. Point mutations of abnormal single stranded conformation were detected by DNA sequencing. The methylation of thePTENpromoter was analyzed by methylation-specific PCR. Expression ofPTENwas detected in 57.5% (84/146) of patients with breast carcinoma. By contrast,PTENexpression was detected in 100% of normal samples. Expression ofPTENwas found to negatively correlate with the tumor size, the pathological stage and the expression of the estrogen receptor (ER) and the progesterone receptor (PR) in breast cancer. The 2-year disease-free survival of patients with a high expression ofPTENwas higher compared with those with lowPTENexpression (P<0.05). Missense mutations in exon 2 ofPTENwere identified in 1/45 breast cancer cases.PTENpromoter methylation was detected in 31.1% (14/45) of breast carcinomas, of which 64.3% (9/14) were associated with a loss ofPTENexpression. The tumor suppressor gene,PTEN, was abnormally expressed in the breast carcinomas. The number ofPTENmutations were low (1/45) in the sporadic breast cancer cases analyzed in the present study andPTENpromoter methylation may have been the main mechanism leading to the decreased expression ofPTEN. These results indicate thatPTENis important for the tumorigenesis, development and prognosis of breast cancer.
Department of Oncology, General Hospital of Beijing Military Area, Beijing 100700;
Hong-Yan
HY
Zhang
Feng
F
Liang
Zhi-Ling
ZL
Jia
San-Tai
ST
Song
Ze-Fei
ZF
Jiang
PTEN gene; breast cancer; gene mutation; promoter methylation