p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma

✍ Scribed by Hirohisa Hirabayashi; Yoshitaka Fujii; Masahiro Sakaguchi; Hisaichi Tanaka; Hyung-Eun Yoon; Yosuke Komoto; Masahiro Inoue; Shinichiro Miyoshi; Hikaru Matsuda

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 395 KB
• Volume: 73
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19971127)73:5<639::aid-ijc5>3.0.co;2-y

✦ Synopsis

There have been few reports on genetic alterations in thymomas. To investigate the expression of p16 INK4A , RB, p53 and cyclin D1 in thymomas, we first examined 36 thymomas (non-invasive type, 16 cases; invasive type, 20 cases) and 3 thymic carcinomas, using immunohistochemistry. Abnormal expression of p16 INK4A , RB, p53 and cyclin D1 was observed in 18, 8, 10 and 7 cases, respectively. Only a subgroup of invasive thymomas and thymic carcinomas showed an inverse correlation between p16 INK4A and RB expression. Subsequently, we examined the 36 thymomas and 4 thymic carcinomas for mutations in p53 and CDKN2 genes, using PCR-SSCP and direct-sequencing analyses. No mutation of these genes was detected in the thymomas and thymic carcinomas examined. A polymorphism in the 3Ј untranslated region of exon 3 of CDKN2 was detected in 5 cases of thymoma. We searched for hypermethylation in the promoter region of CDKN2, observing it in 4 thymomas and 1 thymic carcinoma. Our data suggest that, unlike other more common cancers, alteration of the p53 gene may not play a significant role in the tumorigenesis of thymoma. However, inactivation of p16 INK4A and RB may play a role in the progression of thymoma and thymic carcinoma.