Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
Journal website https://www.jocmr.org

Review

Volume 15, Number 2, February 2023, pages 68-75

Molecular Histopathology for Establishing Diagnostic Method and Clinical Therapy for Ovarian Carcinoma

Figure

Figure 1.
Figure 1. Fallopian tube hypothesis on the origin of high-grade serous carcinoma (HGSC). Fallopian tube epithelium cells of the fimbriated ends undergo initial neoplastic transformation and become serous tubal intraepithelial carcinoma (STIC). STIC cells are resistant to anoikis, which favors settlement and ovarian surface invasion. The ovarian microenvironment, rich in hormonal and inflammatory factors, drives the full neoplastic transformation to invasive high-grade serous carcinoma (HGSC). SCOUT: secretory cell out-growth.

Table

Table 1. Classification, Origin, and Mechanism of Epithelial Ovarian Cancer
 
Tumor typeSerousEndometrioidClear cellMucinous
High gradeLow grade
Borderline malignant tumors are abnormal cells that form in the tissue covering the ovary. They are not cancerous and are generally cured with surgery. Approximately 15 out of 100 ovarian tumors (15-20%) are borderline tumors [11]. They are also described as atypical proliferative tumors and were previously called tumors with low malignant potential [11]. They are different from ovarian cancer because they do not grow into the supportive tissue of the ovary (the stroma). They slowly grow and in a more controlled way than cancer cells. Borderline tumors generally affect women aged between 20 and 40 years. They are usually diagnosed at an early stage when the abnormal cells are still within the ovary. Ovarian atypical endometriosis is a premalignant lesion, and its potential to progress to endometriosis-associated ovarian cancer highlights its significance [12]. In BRCA1/2-associated hereditary breast and ovarian cancer (HBOC), female and male breast and ovarian cancers (including fallopian tube and primary peritoneal cancers) can occur [13]. To a lesser extent, the development of other cancers, such as prostate and pancreatic cancers, is allowed [13]. Melanoma primarily affects individuals with BRCA2 pathogenic variants. The risk of developing associated cancers depends on whether HBOC is caused by BRCA1/2 pathogenic variants. Pathogenic germline variants underlie up to 20% of ovarian carcinoma (OC) cases and are associated with varying degrees of OC risk [14]. For pathogenic mutations in high-penetrance genes, such as BRCA1/2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well established, thus improving the mortality rate [14]. STIC: serous tubal intraepithelial carcinoma; HNF-1β: hepatocyte nuclear factor-1 beta; HGSC: high-grade serous carcinoma; ER: estrogen receptor.
Incidence34%5%16%23%12%
Tissue originFallopian tube epitheliumFallopian tube epitheliumEndometrial cellsEndometrial cellsOvarian surface epithelium
Ovarian surface epitheliumOvarian surface epitheliumOvarian surface epitheliumOvarian surface epitheliumBrenner tumor
Precancerous lesionSTIC [10]Borderline malignant tumor [11]Atypical endometriosis [12]Atypical endometriosisBorderline malignant tumor [11]
Molecular biological abnormalitiesp53 mutationKRAS mutationERa high expressionHNF-1β high expressionKRAS mutation
BRCA1/2 mutationBRAF mutationPI3KCA mutationPI3KCA mutationHER2 high expression
Chromosome instabilityBRCA1/2 mutationCTNNB1 mutationPTEN mutation
ARID1A mutationARID1A mutation
BRCA1/2 mutation
Microsatellite instability
Sensitivity to chemotherapyHighMiddleHighLowLow
HBOC [13, 14]++++++--
RRSO [13, 14]Recommend----
Type I/IIType IIType I
IncidenceEurope, USA > AsiaEurope, USA < Asia