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CDC42-positive macrophages may prevent malignant transformation of ovarian endometriosis
Belen Canet1, Cristina Pons, Inigo Espinosa
1Department of Pathology, Hospital de la Santa Creu i Sant Pau, Institute of Biomedical Research (IIB Sant Pau), Autonomous University of Barcelona, Barcelona -08041, Spain.
Abstract:
It is currently thought that most clear cell and endometrioid carcinomas arise from ovarian endometriosis. We recently suggested that, besides their origin in the ovary, reduction of CDC42 messenger RNA (a member of the RHO GTPase family) may contribute to explain why clear cell carcinomas are not uncommonly found limited to the ovary (stage I). On the other hand, little is known about the expression of CDC42 in ovarian endometriosis with and without carcinoma. Twenty-two endometriotic cysts not associated with carcinoma, 19 endometriotic cysts associated with carcinoma (contiguous endometriosis), as well as the 19 corresponding tumors (11 clear cell, 4 endometrioid, and 4 mixed-clear cell and endometrioid-carcinomas) were investigated. We analyzed CDC42 expression both by real-time polymerase chain reaction and immunohistochemistry. Endometriotic cysts not associated with carcinoma showed higher expression of CDC42 messenger RNA than cysts associated with carcinoma (P = .002). Immunohistochemically, CDC42 was exclusively expressed by macrophages. CDC42-positive macrophages were present in most of the endometriotic cysts not associated with carcinoma (11/19, or 58%). In contrast, only 5 endometriotic cysts containing carcinoma (contiguous endometriosis) (5/18, or 28%) and 1 ovarian carcinoma arising from endometriosis (1/18, or 5%) had CDC42-positive macrophages (58% versus 28%, P = .065; 28% versus 5%, P = .046). Our results raise the possibility that CDC42-positive macrophages may prevent the development of endometrioid and clear cell carcinomas.
Insights
Reduced CDC42 expression in ovarian endometriosis may link to cancer development. CDC42-positive macrophages appear to protect against clear cell and endometrioid carcinomas.
Area of Science:
- Gynecologic Oncology
- Cell Biology
- Immunology
Background:
- Ovarian endometriosis is the suspected origin for most clear cell and endometrioid carcinomas.
- Reduced CDC42 (a RHO GTPase family member) messenger RNA may explain stage I clear cell carcinomas limited to the ovary.
- CDC42 expression in ovarian endometriosis with and without carcinoma is largely unknown.
Purpose of the Study:
- To investigate the expression of CDC42 in ovarian endometriosis with and without associated carcinoma.
- To determine the role of CDC42-positive macrophages in the pathogenesis of ovarian endometriosis-associated carcinomas.
Main Methods:
- Analysis of CDC42 expression in 22 endometriotic cysts without carcinoma, 19 endometriotic cysts with carcinoma, and 19 corresponding ovarian tumors.
- Quantitative assessment using real-time polymerase chain reaction for messenger RNA levels.
- Immunohistochemistry to detect CDC42 protein expression, specifically in macrophages.
Main Results:
- Endometriotic cysts without carcinoma exhibited significantly higher CDC42 messenger RNA expression compared to those with carcinoma (P = .002).
- CDC42 protein was exclusively found in macrophages.
- CDC42-positive macrophages were more prevalent in endometriotic cysts without carcinoma (58%) than in those with carcinoma (28%) or arising carcinomas (5%).
Conclusions:
- A decrease in CDC42 messenger RNA in ovarian endometriosis is associated with the presence of carcinoma.
- The reduced presence of CDC42-positive macrophages in cancerous versus non-cancerous endometriosis suggests a potential protective role.
- CDC42-positive macrophages may play a role in preventing the development of clear cell and endometrioid ovarian carcinomas.
