Dawson, A., Fernandez, M. L., Anglesio, M., Yong, P. J., & Carey, M. S. (2018). Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development. Ecancermedicalscience. https://doi.org/10.3332/ecancer.2018.803
Dawson A, Fernandez ML, Anglesio M, Yong PJ, Carey MS. Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development. Ecancermedicalscience. 2018. doi:10.3332/ecancer.2018.803
Dawson, Amy, et al. "Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development." Ecancermedicalscience, 2018.
For EndNote, Zotero or Mendeley:
Open access
No open license is recorded for this paper. Reuse terms are set by the publisher.
Open Access
Free full text on PubMed Central (PMC5813919)
RRM Academy Synopsis
Endometriosis precedes some ovarian cancers, and overall risk is low
Endometriosis can give rise to some ovarian cancers, and the overall risk of such a cancer stays low. This 2018 narrative review describes molecular studies. Sequencing found shared mutations in endometriosis-associated cancers and the endometriosis beside them. The authors propose that deep infiltrating endometriosis may be a benign neoplasm that invades nearby tissue but seldom spreads far.
Key Findings
Ovarian cancer arose in 0.3–0.8% of patients with a diagnosis of endometriosis in a large epidemiological study. The risk was 2–3 times higher than in controls.
Clear cell and endometrioid ovarian cancers make up approximately 20% of all epithelial ovarian cancers. Only these subtypes have a shown direct clonal link to endometriosis.
A genomic study of deep infiltrating endometriosis found somatic mutations in 79% of 24 cases. Known cancer driver genes carried statistically significant mutations in 26% of all cases screened.
In that study, the driver mutations did not appear to indicate which lesions would progress to a gynecologic cancer. They did not appear to be required for deep infiltrating lesions to develop.
In a 2015 study, 85% of atypical endometriosis lesions showed an immunological gene signature like that of cancer, against 30% of typical endometriosis lesions.
Interpretation
The paper is a narrative review. The authors summarize earlier laboratory, pathology and population studies and report no new data. Tumor sequencing shows shared mutations in endometriosis and adjacent clear cell and endometrioid cancers, which supports the precursor claim. Some cited molecular studies were small, such as an early loss of heterozygosity study of 11 cases. The authors state that the cancer risk of atypical endometriosis without cancer is unknown. They also state that further research on the molecular biology of deep infiltrating endometriosis is warranted.
RRM Context
The review notes that symptom severity does not necessarily match how much disease is present. Many patients receive hormone treatment without surgery, based on suspicion alone. The review names surgery with tissue examination as the gold standard for diagnosis. Restorative reproductive medicine looks for the underlying disease, and excision is the surgical standard for endometriosis. Excision removes the lesion tissue so it can be studied.
Our editorial summary of this paper, not the article's abstract.
Abstract
Endometriosis is a fascinating disease that we strive to better understand. Molecular techniques are shedding new light on many important aspects of this disease: from pathogenesis to the recognition of distinct disease variants like deep infiltrating endometriosis. The observation that endometriosis is a cancer precursor has now been strengthened with the knowledge that mutations that are present in endometriosis-associated cancers can be found in adjacent endometriosis lesions. Recent genomic studies, placed in context, suggest that deep infiltrating endometriosis may represent a benign neoplasm that invades locally but rarely metastasises. Further research will help elucidate distinct aberrations which result in this phenotype. With respect to identifying those patients who may be at risk of developing endometriosis-associated cancers, a combination of molecular, pathological, and inheritance markers may define a high-risk group that might benefit from risk-reducing strategies.
