Loss of heterozygosity on the X chromosome is an independent prognostic factor in ovarian carcinoma: from the Danish "MALOVA" Ovarian Carcinoma Study.
BACKGROUND
Ovarian carcinoma (OC) is the fifth most frequent female cancer type and the fourth most frequent cause of death from cancer among women in Denmark. At the time they are diagnosed with OC, approximately 70% of patients have advanced disease. It is believed that loss of tumor suppressor gene activity plays an important role in the origin and progression of OC and other malignancies. Loss of heterozygosity (LOH) may be detected in individuals heterozygous for an allele and is associated with loss of function of tumor suppressor genes.


METHODS
The polymorphic marker regions (TP53, CACNLB1, D18S58, DXS538, and DXS454) were amplified by polymerase chain reaction followed by separation using gel electrophoresis before LOH was identified. In total, 160 women with primary epithelial OC were included in the study.


RESULTS
Univariate analyses showed significant differences in survival between patients who had advanced OC with LOH or with retention using the microsatellite markers DXS454 (P = 0.04) and DXS538 (P = 0.01). Multivariate Cox regression analysis that included all patients showed that DXS454 (relative hazard [RH] = 3.5; P = 0.002; 95% confidence interval [95% CI], 1.6-7.8), radicality of primary surgery (RH = 5.5; P < 0.0001; 95% CI, 2.7-11.1), and serum tetranectin level (RH = 0.8; P = 0.009; 95% CI, 0.7-0.9) were independent prognostic factors for survival. Multivariate Cox regression analysis restricted to patients with International Federation of Obstetrics and Gynecology Stage III-IV disease showed that DXS454 (RH = 3.4; P = 0.007; 95% CI, 1.4-8.1), radicality of primary surgery (RH = 5.4; P < 0.0001; 95% CI, 2.2-12.9), and serum tetranectin level (RH = 0.8; P = 0.042; 95% CI, 0.7-1.0) were independent prognostic factors.


CONCLUSIONS
LOH at DXS454 (Xq21-q23) appeared to be correlated with reduced survival in patients with OC.
Høgdall
Estrid V S
EV
Department of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. hogdall@dadlnet.dk
Ryan
Andy
A
Kjaer
Susanne K
SK
Blaakaer
Jan
J
Christensen
Lise
L
Bock
Johannes E
JE
Glud
Eva
E
Jacobs
Ian J
IJ
Høgdall
Claus K
CK
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology / Q000601:surgery; D041321:Chromosomes, Human, X / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D003718:Denmark; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D037181:Lectins, C-Type / Q000097:blood; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate
D015220:Calcium Channels; D004273:DNA, Neoplasm; D037181:Lectins, C-Type; C048648:tetranectin