Ribosomal DNA methylation in patients with endometrial carcinoma: an independent prognostic marker.
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.
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. mpowell@msnotes.wustl.edu
Matthew A
MA
Powell
David G
DG
Mutch
Janet S
JS
Rader
Thomas J
TJ
Herzog
Tim Hui-Ming
TH
Huang
Paul J
PJ
Goodfellow
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015139:Blotting, Southern; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018283:Cystadenocarcinoma, Papillary / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000378:metabolism*; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004275:DNA, Ribosomal