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The Korean Journal of Pathology 2010;44(6): 623-630.
doi: https://doi.org/10.4132/KoreanJPathol.2010.44.6.623
Prognostic Significance of Methylation Profiles in Urothelial Carcinomas of the Bladder.
Hee Jung Park, Eui Jin Lee, Sang Yun Ha, Ghee Young Kwon, Young Lyun Oh, Kyoung Mee Kim, Dae Shick Kim, Seongil Seo, Hyun Moo Lee, Han Yong Choi
1Departmentsof Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. bijou@skku.edu, kkmkys@skku.edu
2Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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.
Key Words: Methylation; Urothelial carcinoma; Genes, tumor suppressor; Prognosis