BACKGROUND: Surgery is curative for the majority of patients with endometrial carcinoma: Consequently, the use of adjuvant therapy has been controversial. More effective methods to identify patients who are at risk for recurrence and who would benefit from adjuvant therapy are needed. The objective of this study was to investigate the prognostic significance of ribosomal DNA (rDNA) methylation in patients with endometrial carcinoma. METHODS: rDNA methylation was assessed in 215 endometrial tumors by Southern blot analysis of HpaII-digested DNA using a probe corresponding to the 5.8 and 28S ribosomal subunits. Tumor rDNA methylation status was correlated with patient outcome. RESULTS: The majority of tumors demonstrated high levels of rDNA methylation (rDNA-high; 74%). Both disease free survival and overall survival were significantly worse for patients with low-level rDNA methylation (rDNA-low; P < 0.0001). African-American patients were more likely to have rDNA-low tumors than Caucasian patients (P = 0.002). Among the subpopulation of patients with endometrial carcinoma for whom the use of adjuvant therapy is most controversial (148 women with Stage I-II endometrioid tumors), survival was significantly worse for the patients with rDNA-low tumors (P < 0.0001); and, using multivariate analyses, tumor rDNA level was the only significant prognostic factor for both disease free survival and overall survival (hazard ratios, 11.0 and 26.3, respectively; P < 0.01 for both). CONCLUSIONS: rDNA methylation is an independent prognostic indicator for patients with endometrial carcinoma that may serve to identify women with early-stage disease at who are at high risk for recurrence. Racial differences in DNA methylation may explain the historically observed disparity in survival between African-American patients and Caucasian patients. Copyright 2002 American Cancer Society.
BACKGROUND: Surgery is curative for the majority of patients with endometrial carcinoma: Consequently, the use of adjuvant therapy has been controversial. More effective methods to identify patients who are at risk for recurrence and who would benefit from adjuvant therapy are needed. The objective of this study was to investigate the prognostic significance of ribosomal DNA (rDNA) methylation in patients with endometrial carcinoma. METHODS: rDNA methylation was assessed in 215 endometrial tumors by Southern blot analysis of HpaII-digested DNA using a probe corresponding to the 5.8 and 28S ribosomal subunits. Tumor rDNA methylation status was correlated with patient outcome. RESULTS: The majority of tumors demonstrated high levels of rDNA methylation (rDNA-high; 74%). Both disease free survival and overall survival were significantly worse for patients with low-level rDNA methylation (rDNA-low; P < 0.0001). African-American patients were more likely to have rDNA-low tumors than Caucasian patients (P = 0.002). Among the subpopulation of patients with endometrial carcinoma for whom the use of adjuvant therapy is most controversial (148 women with Stage I-II endometrioid tumors), survival was significantly worse for the patients with rDNA-low tumors (P < 0.0001); and, using multivariate analyses, tumor rDNA level was the only significant prognostic factor for both disease free survival and overall survival (hazard ratios, 11.0 and 26.3, respectively; P < 0.01 for both). CONCLUSIONS: rDNA methylation is an independent prognostic indicator for patients with endometrial carcinoma that may serve to identify women with early-stage disease at who are at high risk for recurrence. Racial differences in DNA methylation may explain the historically observed disparity in survival between African-American patients and Caucasian patients. Copyright 2002 American Cancer Society.
Authors: Ya-Ting Hsu; Fei Gu; Yi-Wen Huang; Joseph Liu; Jianhua Ruan; Rui-Lan Huang; Chiou-Miin Wang; Chun-Liang Chen; Rohit R Jadhav; Hung-Cheng Lai; David G Mutch; Paul J Goodfellow; Ian M Thompson; Nameer B Kirma; Tim Hui-Ming Huang Journal: Clin Cancer Res Date: 2013-09-27 Impact factor: 12.531
Authors: A S Felix; T M Brasky; D E Cohn; D G Mutch; W T Creasman; P H Thaker; J L Walker; R G Moore; S B Lele; S R Guntupalli; L S Downs; Ci Nagel; J F Boggess; M L Pearl; O B Ioffe; W Deng; D S Miller; L A Brinton Journal: Int J Cancer Date: 2017-11-06 Impact factor: 7.396
Authors: Jay E Allard; Gadisetti V R Chandramouli; Katherine Stagliano; Brian L Hood; Tracy Litzi; Yutaka Shoji; Jeff Boyd; Andrew Berchuck; Thomas P Conrads; G Larry Maxwell; John I Risinger Journal: Front Oncol Date: 2012-07-04 Impact factor: 6.244
Authors: A Soubry; Sk Murphy; Z Huang; A Murtha; Jm Schildkraut; Rl Jirtle; F Wang; J Kurtzberg; W Demark-Wahnefried; Mr Forman; C Hoyo Journal: Clin Epigenetics Date: 2011-10-26 Impact factor: 6.551