Is global DNA methylation in sporadic uterine adenocarcinomas in women a result of histological and clinical tumor advancement?

Abstract

Aim: to find out the relationship, if any, between the extent of the overall genomic DNA methylation, and clinical and pathological features of the sporadic endometrial adenocarcinomas in women. Material: genomic DNA was isolated from 44 primary uterine cancer tissue specimens. There were eight G1, 24 G2 and twelve G3 tumors. Methods: m5dC level was estimated after enzymatic digestion of DNA into nucleotides, 32P-postlabelling, twodimensional thin-layer chromatography on cellulose plates and phosphorobioimaging. The overall m5dC of the uterine cancer DNAs expressed as a ratio: (pm5dC/pm5dC+pdC) x 100% was compared to results obtained for parallel investigated but published earlier normal human endometrium DNAs. Results: mean total cancer DNA methylation (3.48±0.46%) was significantly higher than that of the normal proliferative endometrium (2.94±0,4%, p=0.003) and lower than that of the secretory endometrium DNAs (3.75±0,47%, p=0.03). Among all endometrial cancer DNAs six were found to be hypomethylated, eight were hypermethylated, whereas the remaining 30 had m5dC within range of normal endometrium. Total DNA methylation was significantly higher in poorly differentiated (G3) than in lower grade neoplasms (3.94±0.46 vs. 3.3 ±0.32 %, p=0.025). Lower levels of DNA methylation seemed to be associated with diminished tumor invasiveness. Conclusions: our results suggest that alterations in overall DNA methylation seem to be a result of neoplastic transformation and could therefore be used as a prognostic molecular marker of endometrial cancer.