Prognostic and diagnostic relevance of hypermethylated in cancer 1 (HIC1)             CpG island methylation in renal cell carcinoma.
The tumour suppressor gene hypermethylated in cancer 1 (HIC1) is a transcriptional             repressor, which functionally cooperates with p53. Loss of HIC1 function is associated             with the development of various tumor entities. The aim of this study was to elucidate             the relevance of CpG island (CGI) methylation of HIC1 in renal cell carcinoma             (RCC). DNA methylation of HIC1 was analysed in a total of 98 tumor and 70 tumor             adjacent normal specimens. After conducting bisulfite conversion, relative methylation             levels were quantitated using pyrosequencing. Relative methylation values were             compared for paired tumor and normal specimen and for correlation with clinico-pathologic             and follow-up data of patients. Tumor-specific hypermethylation could not be detected             for the subregion of the HIC1 - CGI analyzed in this study. Comparing the level             of methylation in tumors to clinicopathological data solely, patients without             lymph node metastases demonstrated a higher level of methylation compared to patients             with lymph node metastases (p=0.030). Patients recurrence-free survival (p=0.0074)             both in univariate as well as bivariate cox regression analysis. This study identifies             HIC1 hypermethylation in tumors as an independent predictor of reduced recurrence-free             survival, which fits into our current understanding of hypermethylated HIC1 being             a marker for poor prognosis. Therefore, HIC1 - CGI methylation could be a candidate             marker to improve individualized therapy and risk stratification.
Department of Urology, Hannover Medical School, Hannover, Germany.
H
H
Eggers
S
S
Steffens
A
A
Grosshennig
J U
JU
Becker
J
J
Hennenlotter
A
A
Stenzl
A S
AS
Merseburger
M A
MA
Kuczyk
J
J
Serth
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D014408:Biomarkers, Tumor; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors