Aberrant promoter methylation and inactivation of PTEN gene in cervical carcinoma from Indian population

Abstract

PTEN, a tumor-suppressor gene located on chromosome 10q23.3 is implicated in multiple tumors including cervical carcinoma. We examined 135 cervical cancer specimens for PTEN gene expression and promoter methylation using methylation-specific PCR and immunohistochemistry and also studied the mutation in PTEN gene through PCR-single-stranded conformational polymorphism. PTEN expression and its methylation status were also correlated with clinicopathologic parameters. The results showed an abnormal band on exon 5 and exon 9 of the PTEN gene. In PTEN gene, 61% specimen showed methylation. PTEN methylation was found in 39% cases of stage I, 60% of stage II, and 75% of stages III-IV. The correlation between PTEN methylation and clinical stage was found to be statistically significant (P=0.003). Nuclear PTEN expression was detected in 84 of 135 (62%) cases of cervical carcinoma, and the remaining 51 of 135 (38%) cases were observed as expressional loss. The loss of PTEN expression was significantly correlated clinical stage (P=0.001). Loss of PTEN expression was observed in 34 (41%) cases among 83 methylation positive cases, whereas among 52 methylation-negative cases, only 13 (25%) cases were seen as immunostaining negative with the statistically significant value (P=0.05). Promoter methylation and loss of PTEN expression occur frequently in carcinoma of uterine cervix. Our results suggest that PTEN plays an important role in the carcinogenesis of cervical cancer.