p16(INK4) and p15(INK4B) alterations in primary gynecologic malignancy

Abstract

Chromosome 9 abnormalities have been found in primary tumors and cell lines from human gynecologic malignancy. Alterations of p16(INK4) and p15(INK4B) genes mapped on the band p21 of chromosome 9 have been detected in various human tumors, but the role of these genes as tumor suppressors in vivo appear to be dependent on tumor type. Polymerase chain reaction (PCR)- based analysis was performed to search for lesions of these genes in 202 primary gynecologic malignancies. Homozygous deletions of p16(INK4) were detected in 7 of 128 (5%) cervical, 1 of 41 (2%) endometrial, 2 of 27 (7%) ovarian, and 3 of 6 (50%) vulvar carcinomas, while homozygous deletions of p15(INK4B) were detected in 19 of 128 (15%) cervical, 1 of 41 (2%) endometrial, 9 of 27 (33%) ovarian, and 3 of 6 (50%) vulvar carcinomas, respectively. No mutations were found in exon 2 of p16(INK4) from 161 cases of gynecologic malignancy without deletion of p16(INK4). All 3 cases of vulvar carcinoma showing homozygous deletions of p16(INK4) and p15(INK4B) were at advanced clinical stage (stage III-IV), while all 7 cases of cervical carcinoma and 2 cases of ovarian carcinoma showing homozygous deletion of p16(INK4) were at early stage (stage I-II). The results indicate that homozygous deletions of p16(INK4) and/or p15(INK4B) genes may play a role in a subset of primary gynecologic malignancy.