Molecular genetic analysis of endometriosis.

Endometriosis is a very common gynaecological condition in which tissue histologically similar to endometrium proliferates at sites outside the uterine cavity.Oncogenes and tumour suppressor genes are commonly altered in ovarian cancers and the development of endometriosis may involve mutations in the same class of genes.This possibility has been investigated by examining DNA from 14 cases of endometriosis synchronous with ovarian carcinoma and 40 cases of solitary endometriosis for clonal status, alterations in TP53, RASK and MTS1 and allelic losses at candidate ovarian tumour suppressor loci on chromosome arms 2q, 3p, 4p, 41, 5q, 6q, 7p, 9p, 11q, 17p, 17q, 22q and Xq. The majority (82%) of endometriotic cysts were monoclonal, but 8 of 10 normal endometrial glands were also monoclonal demonstrating that endometriosis could develop from by implantation of a single endometrial cell or single endometrial gland or by metaplasia of a single peritoneal cell. Loss of heterozygosity (LOH) analysis of endometriosis cases synchronous with ovarian cancers demonstrated common genomic deletions which were statistically unlikely to have occurred by change and supports the hypothesis that endometriosis is the precursor of all endometrioid and clear cell ovarian cancers. Among the solitary endometriosis cases a total of 14/40 (35%) cases demonstrated LOH at one or more markers. The chromosomes most frequently involved were 9p (21%), 11q (19%) and 22q (19%). LOH on these chromosomes was also demonstrated to occur frequently in early stage and low grade endometrioid ovarian cancers. No mutations were detected in RASK or MTS1 but a TP53 mutation was detected in one endometriotic cyst.This study provides compelling evidence in support of the hypothesis endometriosis can undergo malignant transformation and is the precursor of endometrioid and clear cell ovarian carcinoma and that genetic alterations in tumour suppressor genes is instrumental in the development of all endometriosis.