Identification of allelic losses in benign, borderline, and invasive epithelial ovarian tumors and correlation with clinical outcome.
BACKGROUND
The somatogenetic alterations that lead to the development of benign adenomas, borderline tumors, and invasive ovarian carcinomas are not well understood. This study investigated allelic losses in these three types of ovarian tumors.


METHODS
Twelve genetic regions on chromosomes 2q, 5q, 6p, 6q, 9p, 11q, 17p, 17q, 18q, and 22q were analyzed by polymerase chain reaction for loss of heterozygosity (LOH). The study was performed on formalin fixed, paraffin embedded tissue samples from 72 invasive ovarian carcinomas, 35 ovarian tumors of borderline malignancy, and 25 benign ovarian adenomas.


RESULTS
LOH was found in only 8% of the analyzed adenomas (at 2q21 and 17p13) and 11% of the borderline tumors (at 2q21, 5q21, 6p21, 17p13, and 17q21). Allelic losses were noted for 77.7% of all of the invasive carcinomas analyzed. The frequency of LOH was 56% at a locus near 17p13 (TP53) and 40.5% at 17q21 (BRCA1). LOH was observed in 30.4% of informative cases at 5q21 and in 21.4% at chromosome 18q21. The chromosomal regions 2q21-22 and 9p21 had deletions at frequencies of 32.4% and 25%, respectively. International Federation of Gynecology and Obstetrics stage and the presence of LOH correlated significantly with survival but were not independent predictors of survival. Serous subtypes of invasive carcinoma were significantly more prone to deletions than nonserous tumors.


CONCLUSIONS
The results of this study suggest that LOH occurs only occasionally in adenomas and borderline tumors, whereas it is frequently observed in invasive ovarian carcinomas. Therefore, other genetic events seem to be involved in early ovarian tumor development. However, the presence of multiple allelic losses is an indicator of higher stages of invasive carcinoma.
Saretzki
G
G
Institute of Pathology, University Hospital Charité, Humboldt University Berlin, Germany.
Hoffmann
U
U
Röhlke
P
P
Psille
R
R
Gaigal
T
T
Keller
G
G
Höfler
H
H
Löning
T
T
Petersen
I
I
Dietel
M
M
D000236:Adenoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000483:Alleles; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome