title: p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma.
abstract: There have been few reports on genetic alterations in thymomas. To investigate the expression of p16INK4A, 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 p16INK4A, 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 p16INK4A 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 3' 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 p16INK4A and RB may play a role in the progression of thymoma and thymic carcinoma.
authors.affiliation: First Department of Surgery, Osaka University Medical School, Suita, Japan. hhirabar@surg1.med.osaka-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Hirabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: H E
authors.initials: HE
authors.lastname: Yoon
authors.forename: Y
authors.initials: Y
authors.lastname: Komoto
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Miyoshi
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D015139:Blotting, Southern; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019942:Genes, p16 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016160:Retinoblastoma Protein / Q000378:metabolism; D013945:Thymoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1