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Review
. 2021 Apr 23;22(9):4409.
doi: 10.3390/ijms22094409.

Mechanisms of High-Grade Serous Carcinogenesis in the Fallopian Tube and Ovary: Current Hypotheses, Etiologic Factors, and Molecular Alterations

Isao Otsuka  1
Affiliations
Review

Mechanisms of High-Grade Serous Carcinogenesis in the Fallopian Tube and Ovary: Current Hypotheses, Etiologic Factors, and Molecular Alterations

Isao Otsuka. Int J Mol Sci. .

Abstract

Ovarian high-grade serous carcinomas (HGSCs) are a heterogeneous group of diseases. They include fallopian-tube-epithelium (FTE)-derived and ovarian-surface-epithelium (OSE)-derived tumors. The risk/protective factors suggest that the etiology of HGSCs is multifactorial. Inflammation caused by ovulation and retrograde bleeding may play a major role. HGSCs are among the most genetically altered cancers, and TP53 mutations are ubiquitous. Key driving events other than TP53 mutations include homologous recombination (HR) deficiency, such as BRCA 1/2 dysfunction, and activation of the CCNE1 pathway. HR deficiency and the CCNE1 amplification appear to be mutually exclusive. Intratumor heterogeneity resulting from genomic instability can be observed at the early stage of tumorigenesis. In this review, I discuss current carcinogenic hypotheses, sites of origin, etiologic factors, and molecular alterations of HGSCs.

Keywords: carcinogenesis; high-grade serous carcinoma; molecular alterations; ovarian cancer.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Carcinogenic hypotheses and risk/protective factors. * including menstruation and postmenopausal bleeding.
Figure 2
Figure 2
Etiologic factors of HGSCs. ROS, reactive oxygen species.
Figure 3
Figure 3
A model of high-grade serous carcinogenesis. FTE, fallopian tube epithelium. OSE, ovarian surface epithelium. SBT, serous borderline tumor. LGSC, low-grade serous carcinoma. HGSC, high-grade serous carcinoma.
See this image and copyright information in PMC

References

    1. Prat J., D’Angelo E., Espinosa I. Ovarian carcinomas: At least five different diseases with distinct histological features and molecular genetics. Hum. Pathol. 2018;80:11–27. doi: 10.1016/j.humpath.2018.06.018. - DOI - PubMed
    1. Kurman R.J., Shih I.M. The dualistic model of ovarian carcinogenesis: Revisited, revised, and expanded. Am. J. Pathol. 2016;186:733–747. doi: 10.1016/j.ajpath.2015.11.011. - DOI - PMC - PubMed
    1. Salazar C., Campbell I.G., Gorringe K.L. When Is “Type I” Ovarian Cancer Not “Type I”? Indications of an Out-Dated Dichotomy. Front. Oncol. 2018;8:654. doi: 10.3389/fonc.2018.00654. - DOI - PMC - PubMed
    1. Bowtell D.D. The genesis and evolution of high-grade serous ovarian cancer. Nat. Rev. Cancer. 2010;10:803–808. doi: 10.1038/nrc2946. - DOI - PubMed
    1. Bodurka D.C., Deavers M.T., Tian C., Sun C.C., Malpica A., Coleman R.L., Lu K.H., Sood A.K., Birrel M.J., Ozols R., et al. Reclassification of serous ovarian carcinoma by a 2-tier system. A Gynecologic Oncology Group study. Cancer. 2012;119:3087–3094. doi: 10.1002/cncr.26618. - DOI - PMC - PubMed