Molecular genetic evidence that endometriosis is a precursor of ovarian cancer.
Histopathology and epidemiology studies have consistently demonstrated a strong link between endometriosis and endometriosis-associated ovarian cancers (EAOCs)--in particular, the endometrioid and clear cell subtypes. However, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link because similar factors predispose to both diseases. In order to search for evidence of clonal progression, we analyzed 10 EAOCs (endometrioid=4; clear cell=6) with coexisting endometriosis for common molecular genetic alterations in both the carcinoma and corresponding endometriosis. We used 82 microsatellite markers spanning the genome to examine loss of heterozygosity (LOH) in the coexisting carcinoma and endometriosis samples. A total of 63 LOH events were detected in the carcinoma samples; twenty two of these were also detected in the corresponding endometriosis samples. In each case, the same allele was lost in the endometriosis and cancer samples. Interestingly, no marker showed LOH in the endometriosis alone. These data provide evidence that endometriosis is a precursor to EAOCs.
Prowse
Amanda H
AH
Nuffield Department of Obstetrics and Gynaecology, The Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom. amanda.prowse@obs-gyn.ox.ac.uk
Manek
Sanjiv
S
Varma
Rajesh
R
Liu
Jinsong
J
Godwin
Andrew K
AK
Maher
Eamonn R
ER
Tomlinson
Ian P M
IP
Kennedy
Stephen H
SH
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D004715:Endometriosis / Q000235:genetics / Q000473:pathology*; D005260:Female; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D010049:Ovarian Diseases / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*
D004273:DNA, Neoplasm