Faculty Collaboration Database

Ribosomal DNA methylation in patients with endometrial carcinoma: an independent prognostic marker. Cancer 2002 Jun 01;94(11):2941-52

Date

07/13/2002

Pubmed ID

12115383

DOI

10.1002/cncr.10559

Scopus ID

2-s2.0-0036604045 (requires institutional sign-in at Scopus site)   56 Citations

Abstract

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.

Author List

Powell MA, Mutch DG, Rader JS, Herzog TJ, Huang TH, Goodfellow PJ

Author

Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma, Clear Cell
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Blotting, Southern
Carcinoma, Endometrioid
Cystadenocarcinoma, Papillary
DNA Methylation
DNA, Neoplasm
DNA, Ribosomal
Down-Regulation
Endometrial Neoplasms
Female
Humans
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Survival Rate