Mechanisms of inactivation of the p16INK4a gene in leiomyosarcoma of soft tissue: decreased p16 expression correlates with promoter methylation and poor prognosis

• DOI: 10.1002/path.1419
• Publication Date: 2003-10-28T08:00:42Z
• Authors: Ken‐ichi Kawaguchi; Yoshinao Oda; Tsuyoshi Saito; Hidetaka Yamamoto; Sadafumi Tamiya; Tomonari Takahira; Kimitaka Miyajima; Yukihide Iwamoto; Masazumi Tsuneyoshi
• Keywords: Adult; Aged, 80 and over; Leiomyosarcoma; Male; Adolescent; Genes, p16; DNA Mutational Analysis; Homozygote; Middle Aged; Immunohistochemistry; Methylation; Neoplasm Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; 0302 clinical medicine; Humans; Female; Genes, Tumor Suppressor; Child; Cyclin-Dependent Kinase Inhibitor p16; Gene Deletion; Aged

Abstract The p16 INK4a tumour suppressor gene, encoding protein, plays a crucial role in regulation of the G1 cell‐cycle phase. To investigate potential soft tissue leiomyosarcoma (LMS), an immunohistochemical analysis was performed 77 LMSs for expression. Decreased expression protein identified 25 (32%). correlated significantly with large size ( p = 0.0038). In univariate analysis, and decreased were statistically significant adverse prognostic factors 0.025 0.0021, respectively). multivariate including conventional clinicopathological parameters, revealed as only independent unfavourable factor 0.012). elucidate mechanisms inactivation 49 which genomic DNA available examined; homozygous deletion, mutation, promoter hypermethylation conducted using differential PCR, PCR–SSCP, methylation‐specific respectively. Promoter detected 11 LMS cases (22%); deletion 3 (6%); mutation not recognized any studied. Eight 15 (53%) methylation gene promoter. closely poor prognosis 0.0014 0.0088, These results suggest that can be considered reliable parameter patients LMS. Furthermore, more frequent than either or this tumour, also shown to have strong association gene. Copyright © 2003 John Wiley & Sons, Ltd.