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KMID : 0357920100440060623
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Korean Journal of Pathology
2010 Volume.44 No. 6 p.623 ~ p.630
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Prognostic Significance of Methylation Profiles in Urothelial Carcinomas of the Bladder
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Park Hee-Jung
Lee Eui-Jin
Ha Sang-Yun
Kwon Ghee-Young
Oh Young-Lyun
Kim Kyoung-Mee
Kim Dae-Shick
Seo Seong-Il
Lee Hyun-Moo
Choi Han-Yong
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Abstract
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Background : Study on epigenetics of urothelial carcinomas has expanded and allowed better understanding of their correlation with clinicopathologic features. The aim of this study was to determine reliable predictive epigenetic markers for patients with urothelial carcinoma of urinary bladder.
Methods : In 64 urothelial carcinomas of the urinary bladder, methylationspecific polymerase chain reaction with RAS association domain family 1A (RASSF1A), adenomatous polyposis coli (APC), death-associated protein-kinase (DAPK), runt-related transcription factor 3 (RUNX3), p14, p16 and MGMT was performed and correlated the results with p53 mutations, DNA ploidy, clinicopathologic parameters and recurrences.
Results : Hypermethyation of RASSF1A, APC, DAPK, RUNX3, p14, p16 and MGMT promoters was observed in 35 (54.7%), 29 (45.3%), 18 (28.1%), 18 (28.1%), 9 (14.1%), 2 (3.1%), and 6 (9.4%) cases, respectively. Hypermethylation of RUNX3 and APC was significantly associated with high histologic grades and aneuploidy. Methylation of DAPK was significantly associated with muscle invasion. Methylation of DAPK and RUNX3 genes was significantly associated with recurrence. In survival analyses, methylation of RUNX3 gene and methylation-high (methylation at two or more loci) phenotype was significantly associated with poor recurrence-free survival.
Conclusions : Methylation of RUNX3 gene and methylation-high phenotype are significant indicator of recurrence.
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KEYWORD
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Methylation, Urothelial carcinoma, Genes, tumor suppressor, Prognosis
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