Is endometriosis metastasizing? Shared somatic alterations suggest common origins across endometriotic lesions

Objectives Recent studies have shown that multiple forms of endometriosis harbor somatic cancer-driver alterations. Their ultimate function in the pathobiology of endometriosis still remains unclear. However, somatic alterations provide a useful tool for understanding the etiology of endometriosis. Our analysis seeks to address whether anatomically defined endometriosis types can share a common origin or whether each represents a distinct disease type.

Materials and methods We examined endometriosis from 27 women with multiple anatomically separated lesions, and each having at least two distinct types of endometriosis. We assayed these samples with a high sensitivity targeted sequencing panel and validated findings using droplet digital PCR and mutation-surrogate IHC.

Results We studied 73 endometriosis lesions from 27 women and were able to identify somatic cancer driver mutations in 13 cases including alterations in KRAS, NRAS, CTNNB1, EGFR, ERBB2 and PIK3CA. The identified alterations suggest clonality between anatomically separate endometriotic lesions in 8 of 13 cases. In 6 cases our analysis revealed multiple apparently functionally redundant mutations within one gene.

Conclusions Our results suggest clonality between lesions is not uncommon, and site/microenvironment is likely to have a strong influence on the clinical presentation of endometriosis and its malignant potential. Complex redundant alterations suggest multiple lineages and that dissemination is likely to be composed of multiple cells travelling together. Furthermore, our findings suggest that the current anatomically defined classification of endometriosis is not consistent with the etiology of the disease and should be adjusted, taking into account genomic and other molecular markers.

Publication History

Article published online:
07 October 2020