Recent Concepts of Ovarian Carcinogenesis: Type I and Type II

Abstract

Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC) arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT). With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs) of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ), undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.

Ovarian carcinoma: An overview of current status

“…The overall benefits and harm of oral contraceptives depend on the duration of use and time [42,43] . The gene expression profile involves genetic instability with the mutation of genes (PTEN, AR1D1A, CTNNB1, KRAS, BRAF, ERBB2, TP53), over expression of genes (HNF-1 beta, HER2/neu, AKT, HLA-G, APO-E), or microsatellite instability that is associated with type I and type II ovarian tumors [18] . Women being treated for infertility are highly prone to experiencing ovarian carcinoma due to the increased levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) [44,45] .…”

“…A better model of two broad categories, namely type I and type II of ovarian carcinogenesis, has provided the basis of new histopathological, molecular, and genetic studies [18] . Type I tumors are slow-growing indolent neoplasms, and arise from a well-defined precursor, atypical hyperplasia.…”

“…Antibody therapy, immune checkpoint inhibitors, vaccine strategies, adoptive cell therapy, and combinatorial immunotherapy are all used for the treatment of the disease [16] . There are numerous review papers discussing ovarian carcinoma's origin and its development [17] , types and subtypes [13,18] , diagnosis [19,20] , prognosis [21] , and treatment [16,[22][23][24] . As such, there is a need to review and update existing information on ovarian carcinoma.…”

Opportunistic salpingectomy for prevention of sporadic ovarian cancer — a jump from basic science to clinical practice?

“…Exposure of the fimbrial end to the locally elevated inflammatory cytokines at ovulation may trigger development of precursor lesions and malignant transformation by selection of p53 mutations in epithelial cells, which are clonally stimulated to expand [5][6][7]. In turn, telomere shortening occurs and enhances the basal epithelium for transformation and development of dysplasia.…”

BRCA1 Mutation Leads to Deregulated Ubc9 Levels which Triggers Proliferation and Migration of Patient-Derived High Grade Serous Ovarian Cancer and Triple Negative Breast Cancer Cells

“…Epithelial ovarian cancers are typically of the serous subtype and can be subdivided into two categories: Type I and Type II tumors. Type I is considered a low-grade tumor, whereas type II is considered a high-grade tumor; type II is the most malignant form of ovarian cancer accounting for up to 70% of all ovarian cancer diagnoses [3]. The most common and aggressive histotype of epithelial ovarian cancer (EOC), high grade serous carcinoma (HGSOC) is associated with germ line BRCA1 mutations with a lifetime risk of 40-60% [4].…”