Prognostic Significance of Methylation Profiles in Urothelial Carcinomas of the Bladder
박희정, 이의진, 하상윤, 권기영, 오영륜, 김경미, 김대식, 서성일, 이현무, 최한용,
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박희정 ( Park Hee-Jung )
성균관대학교 의과대학 삼성서울병원 병리학교실
이의진 ( Lee Eui-Jin )
성균관대학교 의과대학 삼성서울병원 병리학교실
하상윤 ( Ha Sang-Yun )
성균관대학교 의과대학 삼성서울병원 병리학교실
권기영 ( Kwon Ghee-Young )
성균관대학교 의과대학 삼성서울병원 병리학교실
오영륜 ( Oh Young-Lyun )
성균관대학교 의과대학 삼성서울병원 병리학교실
김경미 ( Kim Kyoung-Mee )
성균관대학교 의과대학 삼성서울병원 병리학교실
김대식 ( Kim Dae-Shick )
성균관대학교 의과대학 삼성서울병원 병리학교실
서성일 ( Seo Seong-Il )
성균관대학교 의과대학 삼성서울병원 비뇨기과학교실
이현무 ( Lee Hyun-Moo )
성균관대학교 의과대학 삼성서울병원 비뇨기과학교실
최한용 ( Choi Han-Yong )
성균관대학교 의과대학 삼성서울병원 비뇨기과학교실
KMID : 0357920100440060623
Abstract
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.
키워드
Methylation; Urothelial carcinoma; Genes; tumor suppressor; Prognosis
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