Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

• Published in: International journal of cancer Vol. 119; no. 3; pp. 556 - 562
• Main Authors: Prowse, Amanda H., Manek, Sanjiv, Varma, Rajesh, Liu, Jinsong, Godwin, Andrew K., Maher, Eamonn R., Tomlinson, Ian P.M., Kennedy, Stephen H.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2006; Wiley-Liss
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - pathology; Adult; Aged; Biological and medical sciences; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - pathology; clear cell ovarian cancer; DNA, Neoplasm - genetics; endometrioid ovarian cancer; endometriosis; Endometriosis - genetics; Endometriosis - pathology; Female; Female genital diseases; Genome, Human; Gynecology. Andrology. Obstetrics; Humans; Loss of Heterozygosity; Medical sciences; Microsatellite Repeats; Middle Aged; Ovarian Diseases - genetics; Ovarian Diseases - pathology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Polymerase Chain Reaction - methods; Precancerous Conditions - genetics; Precancerous Conditions - pathology; precursor lesions; Tumors; Human; Allelic imbalance; Premalignant lesion; Ovary cancer; Endometriosis; clear cell ovarian cancer; Malignant tumor; Female genital diseases; Ovarian diseases; Clear cell carcinoma; Cancerology; precursor lesions; Loss of heterozygosity; Uterine diseases; Cytogenetics; Genetics; endometrioid ovarian cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21845

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. © 2006 Wiley‐Liss, Inc.