Investigator
Nosm University
Low-grade serous ovarian carcinoma: an evolution toward targeted therapy
Low-grade serous ovarian carcinoma and its high-grade serous ovarian carcinoma counterpart differ in their precursor lesions, molecular profile, natural history, and response to therapies. As such, low-grade serous ovarian carcinoma needs to be studied separately from high-grade serous ovarian carcinoma, despite challenges stemming from its rarity. A deeper understanding of the pathogenesis of low-grade serous ovarian carcinoma and the most common molecular defects and pathways involved in the carcinogenesis of the ovarian epithelium from normal to serous borderline ovarian tumors to low-grade serous ovarian carcinoma will help develop better therapies. By adopting targeted approaches there may be an opportunity to integrate novel therapies without the need for robust numbers in clinical trials. This manuscript will discuss low-grade serous ovarian carcinoma and focus on the arising treatments being developed with an improved understanding of the pathogenesis of this disease.
A systematic review and meta-analysis of hormone receptor expression in low-grade serous ovarian carcinoma
Serous ovarian carcinoma is the most common histological type of ovarian cancer, with high-grade serous ovarian carcinoma (HGSOC) being more common than low-grade serous ovarian carcinoma (LGSOC). Despite pathogenic and clinical differences, both grades of serous ovarian carcinoma share the propensity to express receptors for the female hormones - oestrogen (ERs) and progesterone receptors (PRs) - albeit in differing frequencies. Systematic review and meta-analysis of studies reporting the expression of hormone receptors in LGSOC, and comparison with expression in HGSOC. Expression of ERs is observed in 80.7 % of patients with LGSOC [95 % confidence interval (CI) 72.2-89.1 %] and 61.5 % of patients with HGSOC (95 % CI 38.8-84.1 %). Expression of PRs is observed in 54.4 % of patients with LGSOC (95 % CI 44.3-64.4 %) and 30.7 % of patients with HGSOC (95 % CI 15.7-45.7 %). A higher percentage of LGSOCs are positive for ER expression compared with HGSOCs. Similarly, a higher percentage of LGSOCs are positive for PR expression, although PR expression is lower than ER expression. Expression of hormone receptors may represent a therapeutic opportunity for treatment with agents that block their activity, especially in LGSOC which is less responsive to chemotherapy and therapeutic options are limited.
3q26 Amplifications in Cervical Squamous Carcinomas
Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, PIK3CA. The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer. Methods: Published genomic data and associated clinical data from TCGA cervical cancer cohort were analyzed at cBioportal for amplifications in genes at 3q26. The clinical and molecular characteristics of the group of patients with 3q26 amplifications was compared with the group without 3q26 amplifications. Comparative prevalence of amplification and expression of genes at 3q26 in amplified squamous cervical cancer cases were surveyed as well as 3q26 amplifications in cervical cancer cell line databases. Results: Amplification of 3q26 locus is a prevalent molecular lesion in cervical squamous cell carcinomas encountered in about 15% of cases in TCGA cohort of 247 patients. Cancer-related genes commonly amplified from 3q26 include PIK3CA, TBL1XR1, DCUN1D1, SOX2, MECOM, PRKCI, and TERC. Amplified cases do not completely overlap with PIK3CA mutant cases. Differences exist between 3q26-amplified and non-amplified carcinomas in the frequency of mutations and frequency of other amplifications. Most commonly over-expressed genes in 3q26 amplified cases include PIK3CA, TBL1XR1, DCUN1D1, and less commonly SOX2 and PRKCI. Conclusion: The subset of squamous cervical carcinomas with 3q26 amplifications is not overlapping with cancers carrying PIK3CA mutations and contains, besides PIK3CA, other cancer-associated genes that are over-expressed at the mRNA level, including TBL1XR1 and DCUN1D1. DCUN1D1, a regulator of SCF ubiquitin ligase activity, may be a relevant pathogenic player given the importance of ubiquitination and the proteasome in the disease. These observations could form the basis for therapeutic exploitation in this subset of squamous cervical carcinomas.
