Genetic and Pathologic aspects of Maligant Transformation of Endometriosis: Endometriosis-Related Ovarian Cancers-ERON's - Ayse Ayhan, MD

Endometriosis and Endometriosis-Related Ovarian Cancers

Key Points

Information for the presentation: In the 2020 Endofound Medical Conference, Dr. Ayse Ayhan presented about endometriosis (endometrioma)-related ovarian cancer (ERON). Dr. Ayhan is a Consultant Pathologist at Seirei Mikatahara Hospital and lectures on gynecologic and breast pathology at Hamamatsu and Hiroshima Universities Schools of Medicine in Japan, and also has been involved in research as an adjunct faculty at Johns Hopkins University Department of Pathology. 

Importance:

• Endometrioma is highly associated with ovarian cancers, such as clear cell ovarian carcinoma, endometrioid ovarian carcinoma, and seromucinous neoplasms.

Highlights:

• Endometriosis (particularly endometrioma)-related ovarian cancer (ERON) share unique characteristics with endometriosis including their origin and molecular alterations.
• Dr. Ayhan suggests that patients should be aware of the higher risk of ERONs when they have "endometrioma", not endometriosis.

Remarks:

• Endometriosis is highly associated with ovarian cancer incidence. Especially in Asia areas, there is a 4-fold increase of ovarian cancer incidence in endometriosis patients compared to the control.
• ERONs, which include clear cell ovarian carcinoma, endometrioid ovarian carcinoma, and seromucinous borderline tumors, are most likely arise from endometrioma.
• Transcriptome analysis showed that those cancer cells mimic more endometrial cells than ovarian epithelial cells suggesting their origins are from endometrial-like cells.
• They share molecular alterations (PTEN, PI3KCA, and ARID1A) and these alterations are very different from those from other ovarian cancer subtypes.
• These mutation rates are increased as ages, menstruation, and inflammation.
• One of the possible explanations is the Fenton reaction which induces reactive oxygen species and oxidative stress (ROS).
• ROS may persistently cause DNA damage and their accumulation contributes to oncogenic mutations.
• Several molecular targeted therapies are available along with standard chemotherapy and those effects are under evaluation.

Lay Summary

In the 2020 Endofound Medical Conference, Dr. Ayse Ayhan presented about endometriosis (endometrioma)-related ovarian cancer (ERON).

Based on the current understanding of the epidemiology, histology, and molecular alterations, it seems clear that endometriosis is highly related to ERONs.

Endometriosis is highly associated with ovarian cancer incidence. Especially in Asia areas, there is a 4-fold increase of ovarian cancer incidence in endometriosis patients compared to the control.

ERONs, which include clear cell ovarian carcinoma, endometrioid ovarian carcinoma, seromucinous borderline tumors, are most likely arise from endometrioma. Transcriptome analysis showed that those cancer cells mimic more endometrial cells than ovarian epithelial cells suggesting their origins are from endometrial-like cells.

They share molecular alterations and these alterations are very different from those from other ovarian cancer subtypes. The most frequently mutated genes are PTEN (loss), PI3KCA, and ARID1A. PTEN and PI3KCA participate in the PI3K/AKT/mTOR pathway which promotes cell growth and proliferation. ARID1A, a component of the SWI/SNF chromatin remodeling complex, is known to affect RNA polymerase II and participate in DNA repair.

Although they are oncogenic mutations, those occur in histologically normal endometrium. And those mutation rates are increased as ages, menstruation, and inflammation. One of the possible explanations is the Fenton reaction which induces reactive oxidative stress (ROS). ROS may persistently cause DNA damage and their accumulation contributes to oncogenic mutations.

Several molecularly targeted therapies are available along with standard chemotherapy and those effects are under evaluation.

Then, how to inform patients? Dr. Ayhan suggests that patients should aware of the higher risk of ERONs when they have Endometrioma, not endometriosis.

Research Source: https://www.endofound.org/genetic-and-pathologic-aspects-of-maligant-transformation-of-endometriosis-endometriosis-related-ova?pop=mc