DNA ploidy, nuclear size, proliferation index and DNA-hypomethylation in ovarian cancer.
OBJECTIVE
The present study was undertaken to analyze the impact of epigenetic alterations with a main focus on nuclear area, aneuploidy, hyperploidy, and proliferation in 70 ovarian cancer specimens.


METHODS
Morphometric changes and somatic chromosomal ploidy status were assessed by Feulgen spectrophotometry. DNA-hypomethylation of LINE1 repeats was analyzed by means of MethyLight PCR, and methylation levels of satellite 2 (Sat2) and satellite alpha (Satα) DNA sequences in chromosome 1 were measured by Southern blot analysis. These parameters were analyzed with regard to correlations as well as to recurrence and survival.


RESULTS
We identified a significant association between LINE1 DNA-hypomethylation and patient age (p=0.029). Furthermore, LINE1 DNA-hypomethylation was positively correlated with the nuclear area (r=0.47; p<0.001) and the proliferation index (r=0.36; p<0.001). Univariate survival analysis showed that the nuclear area and LINE1 DNA-hypomethylation were prognostic factors for overall (p=0.015 and =0.006, respectively) and progression-free survival (p=0.020 and p=0.001 respectively), the percentage of aneuploidy only for overall survival (p=0.031). Subgroup survival analyses revealed that the prognostic value of these factors is strictly confined to mucinous cancers. In serous cancers no prognostic value could be pointed out for any analyzed parameter. Multivariate analysis of the entire cohort showed that the percentage of hyperploidy was an independent prognostic parameter for overall survival (p=0.003) and LINE1 DNA-hypomethylation for progression-free survival (p=0.03). In mucinous cancers nuclear area and LINE1 DNA-hypomethylation were found to be independent predictors of progression-free and overall survival.


CONCLUSIONS
In this study we identified the correlations between early cancer-associated genome DNA-hypomethylation, nuclear morphometric changes, somatic chromosomal ploidy status and the proliferation index. Prognostic relevance of nuclear area and LINE1 DNA-hypomethylation was revealed exclusively in mucinous ovarian cancers.
Department of Gynecology and Obstetrics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria, Austria.
Alain G
AG
Zeimet
Heidi
H
Fiegl
Georg
G
Goebel
Francis
F
Kopp
Claude
C
Allasia
Daniel
D
Reimer
Ilona
I
Steppan
Elisabeth
E
Mueller-Holzner
Melanie
M
Ehrlich
Christian
C
Marth
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048708:Cell Growth Processes / Q000502:physiology; D053145:Cell Nucleus Size / Q000502:physiology; D002878:Chromosomes, Human, Pair 1; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D042822:Genomic Instability; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D011003:Ploidies; D055815:Young Adult
D004273:DNA, Neoplasm
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