Abstract
Simple SummaryDriver gene mutations have been identified in not only various types of endometriosis which are considered the origin of endometriosis-associated ovarian cancer but also the normal endometrium which is considered the origin of endometriosis. We focused on genomic linkage from normal endometrium to ovarian endometriosis and endometriosis-associated ovarian cancer (EAOC) and summarized the current knowledge of the commonality and differentiation of genomic features in the uterine endometrium, endometriosis, and EAOC. In addition, we have proposed molecular mechanism of ovarian carcinogenesis from the normal endometrium via endometriosis based on genomic alterations. This review is expected to contribute to research for the prevention of endometriosis and EAOC.Numerous epidemiological and histopathological studies support the notion that clear cell and endometrioid carcinomas derive from ovarian endometriosis. Accordingly, these histologic types are referred to as “endometriosis-associated ovarian cancer” (EAOC). Although the uterine endometrium is also considered an origin of endometriosis, the molecular mechanism involved in transformation of the uterine endometrium to EAOC via ovarian endometriosis has not yet been clarified. Recent studies based on high-throughput sequencing technology have revealed that cancer-associated gene mutations frequently identified in EAOC may exist in the normal uterine endometrial epithelium and ovarian endometriotic epithelium. The continuum of genomic alterations from the uterine endometrium to endometriosis and EAOC has been described, though the significance of cancer-associated gene mutations in the uterine endometrium or endometriosis remains unclear. In this review, we summarize current knowledge regarding the molecular characteristics of the uterine endometrium, endometriosis, and EAOC and discuss the molecular mechanism of cancer development from the normal endometrium through endometriosis in an effort to prevent EAOC.
Highlights
Epithelial ovarian cancer involves five major histological types: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous ovarian carcinomas, and the origin of ovarian cancer varies by histological type (the World Health Organization (WHO) classification of tumors of the female genital tract)
We summarize the current knowledge on the commonality and differentiation of genomic features in the uterine endometrium, endometriosis, and endometriosis-associated ovarian carcinoma” (EAOC) and describe a proposed molecular mechanism of EAOC development from the normal endometrium via endometriosis based on genomic alterations
Several genomic studies based on next-generation sequencing data have demonstrated that ARID1A and PIK3CA mutations frequently coexist in both cell carcinoma (CCC) (20–56%) [29] and endometrioid carcinoma (EC) (11–25%) [21,22]
Summary
Epithelial ovarian cancer involves five major histological types: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous ovarian carcinomas, and the origin of ovarian cancer varies by histological type (the World Health Organization (WHO) classification of tumors of the female genital tract) (http://whobluebooks.iarc. fr/editorialboard/index.php, accessed on: 21 March 2021). Based on clinicopathological and epidemiological findings, the precursor of ovarian clear cell carcinoma (CCC) and ovarian endometrioid carcinoma is endometriosis [2,3,4,5,6]. In 1927, Dr Sampson proposed that fragments of the menstrual endometrium flow retrograde through the fallopian tubes and implant at peritoneal surfaces, and this theory is broadly accepted [10]. Another leading theory, the coelomic metaplasia theory, suggests that endometriosis originates from metaplasia of the abdominal peritoneum, as stimulated by hormonal, environmental, or infectious stimuli [11]. We summarize the current knowledge on the commonality and differentiation of genomic features in the uterine endometrium, endometriosis, and EAOC and describe a proposed molecular mechanism of EAOC development from the normal endometrium via endometriosis based on genomic alterations
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