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Review
. 2024 May 30;14(6):704.
doi: 10.3390/life14060704.

Genetic Links between Endometriosis and Endometriosis-Associated Ovarian Cancer-A Narrative Review (Endometriosis-Associated Cancer)

Tanja Pejovic  1 , Ann M Cathcart  2 , Rofieda Alwaqfi  3 , Marjorie N Brooks  1 , Rachel Kelsall  4 , Farr R Nezhat  3   5   6
Affiliations
Review

Genetic Links between Endometriosis and Endometriosis-Associated Ovarian Cancer-A Narrative Review (Endometriosis-Associated Cancer)

Tanja Pejovic et al. Life (Basel). .

Abstract

Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma-EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC.

Keywords: ARD1A; cancer; clear-cell carcinoma; endometrioid adenocarcinoma; endometriosis; ovarian cancer.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Subtypes of epithelial ovarian cancer arise from distinct precursor lesions. dMMR: Deficient mismatch repair. HRD: Homologous recombination deficiency. CI: Chromosomal instability.
Figure 2
Figure 2
A 4.8 cm ovarian mass showing transition from simple cyst lining to papillary and glandular outgrowth (H&E, 10× mag) (A). Areas of the cyst lining showing endometriosis (left side) transforming into atypical endometrial (endometriosis with atypical hyperplasia) (H&E, 50× mag) (B). Endometrioid carcinoma, FIGO grade 1, arising adjacent to the atypical endometriosis (H&E, 200× mag) (C).
See this image and copyright information in PMC

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