Methylation of p16(INK4A) in primary gynecologic malignancy

The p16(INK4A) gene mapped on band p21 of chromosome 9 can be inactivated v ia multiple mechanisms including homozygous deletion, point mutation and pr omoter hypermethylation in various human tumors. A polymerase chain reactio n (PCR) based analysis was performed to examine methylation of the p16(INK4 A) gene promoter in 196 primary gynecologic malignancies including 98 cervi cal, 49 endometrial and 49 ovarian carcinomas. Methylation of p16(INK4A) wa s detected in 31% of cervical, 20% of endometrial, and 4% of ovarian carcin omas, respectively. The incidence of p16(INK4A) methylation in patients wit h cervical and endometrial carcinomas at advanced stages (stages III-IV) wa s statistically higher than those at early stages (stages I-II). There were also significant differences in the incidence of p16(INK4A) methylation in both cancers between the patients who had died of their disease or were al ive with evidence of disease, and those without evidence of disease. The re sults indicate that methylation of the p16(INK4A) gene is present in a prop ortion of primary gynecologic malignancies and this alteration may be assoc iated with poor outcome in cervical and endometrial carcinomas. (C) 1999 Pu blished by Elsevier Science Ltd. All rights reserved.