Molecular staging of gynecological cancer: What is the future?

Binder, Pratibha; Prat, Jaime; Mutch, David G.

doi:10.1016/j.bpobgyn.2015.01.008

Cited by 9 publications

(3 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With a frequency of 70%, the most common ovarian cancer is high-grade serous carcinoma (which originates from serous tubal intraepithelial carcinomas in the Fallopian tubes). This is followed by endometrioid carcinoma and clear-cell carcinoma (both of which originate from endometrial cells), at 10% frequency each, and then low-grade serous carcinoma (which originates from benign lesion in the ovary) and mucinous carcinoma (which originates from gastrointestinal tissue), at 5% of all epithelial cancers (Binder et al, 2015 ; Prat, 2015 ; Ramalingam, 2016 ). High-grade serous ovarian carcinoma carries TP53 mutations, while low-grade serous ovarian carcinoma has wild-type TP53 , but mutations in K-RAS, B-RAF , and other oncogenes (Rojas et al, 2016 ).…”

Section: Hormone-dependent Cancersmentioning

confidence: 99%

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

2017

View full text Add to dashboard Cite

Endometrial and ovarian cancers predominately affect women after menopause, and are more frequently observed in developed countries. These are considered to be hormone-dependent cancers, as steroid hormones, and estrogens in particular, have roles in their onset and progression. After the production of estrogens in the ovary has ceased, estrogen synthesis occurs in peripheral tissues. This depends on the cellular uptake of estrone-sulfate and dehydroepiandrosterone-sulfate, as the most important steroid precursors in the plasma of postmenopausal women. The uptake through transporter proteins, such as those of the organic anion-transporting polypeptide (OATP) and organic anion-transporter (OAT) families, is followed by the synthesis and action of estradiol E2. Here, we provide an overview of the current understanding of this intracrine action of steroid hormones, which depends on the availability of the steroid precursors and transmembrane transporters for precursor uptake, along with the enzymes for the synthesis of E2. The data is also provided relating to the selected transmembrane transporters from the OATP, OAT, SLC51, and ABC-transporter families, and the enzymes involved in the E2-generating pathways in cancers of the endometrium and ovary. Finally, we discuss these transporters and enzymes as potential drug targets.Keywords: sulfatase, aromatase, 17beta-hydroxysteroid dehydrogenase, transporters, OATP, ABC-transporter HORMONE-DEPENDENT CANCERSSteroid hormones have important roles in human physiology, and the disruption of androgen, estrogen, and progesterone actions are implicated in the development of hormone-dependent cancers and benign hormone-dependent diseases. Hormone-dependent cancers include prostate, breast, endometrial, and ovarian cancers, which comprise more than 20% of all cancers in humans, and more than 35% of cancers in women (Ferlay et al., 2013). Indeed, in women, breast cancer is the most frequent cancer in the developed world. In 2012, 1,671,149 new cases of breast cancer were estimated worldwide, with 521,907 associated deaths. In the developed world, endometrial cancer is the most common among gynecological cancers. Worldwide, there were 319,605 new cases and 76,160 deaths from endometrial cancer in 2012 alone (Ferlay et al., 2013). The most deadly of the hormone-dependent cancers is ovarian cancer. Worldwide, there were 238,719 new cases and 151,905 deaths from ovarian cancer in 2012 (Ferlay et al., 2013).

show abstract

Section: Hormone-dependent Cancersmentioning

confidence: 99%

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

2017

View full text Add to dashboard Cite

show abstract

“…EEC is pathologically staged with the International Federation of Gynecology and Obstetrics (FIGO) system [ 2 ]. However, molecular characteristics have not been validated to help predict operative staging of EEC patients at the time of clinical diagnosis [ 10 , 11 ]. Since molecular abnormalities predispose the manifestation of microscopic appearance and drive tumor progression, molecular biomarkers not only provide an opportunity for early detection but also offer the ability to direct therapeutic strategies; both are distinctive from the current microscopic analysis.…”

Section: Introductionmentioning

confidence: 99%

Predicting high-risk endometrioid carcinomas using proteins

Yates

et al. 2018

Oncotarget

View full text Add to dashboard Cite

BackgroundThe lethality of endometrioid endometrial cancer (EEC) is primarily attributable to advanced-stage diseases. We sought to develop a biomarker model that predicts EEC surgical stage at the time of clinical diagnosis.ResultsPSES was significantly correlated with surgical stage in the TCGA cohort (P < 0.0001) and in the validation cohort (P = 0.0003). Even among grade 1 or 2 tumors, PSES was significantly higher in advanced than in early stage tumors in both the TCGA (P = 0.005) and MD Anderson Cancer Center (MDACC) (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in advanced stage tumors.MethodsUsing reverse-phase protein array expression profiles of 170 antibodies for 210 EEC cases from TCGA, we constructed a Protein Scoring of EEC Staging (PSES) scheme comprising 6 proteins (3 of them phosphorylated) for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MDACC using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used.ConclusionsPSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.

show abstract

“…These are indolent tumors arising from premalignant lesions and are associated with KRAS and BRAF mutations. The more common type II EOCs are high‐grade malignancies, commonly diagnosed at an advanced stage, and associated with p53 mutations …”

Section: Molecular Profiling In the Clinical Setting And The Role Of mentioning

confidence: 99%

Frontline treatment of epithelial ovarian cancer

Goh

Mohan

Ladwa

et al. 2015

Asia-Pac J Clncl Oncology

View full text Add to dashboard Cite

This is a contemporaneous review of the frontline treatment of epithelial ovarian cancer (EOC), specifically on the importance of optimal surgical cytoreductive surgery, the pivotal role of platinum-based adjuvant chemotherapy (which encompasses intraperitoneal and dose-dense regimens) and the emergence of neo-adjuvant chemotherapy. Additionally, the benefit of concurrent and maintenance bevacizumab in the suboptimally debullked stage III and stage IV EOC setting is also reviewed. The article also discusses the increasing importance of prognostic and predictive molecular biomarkers in the future management of EOC.

show abstract

Molecular staging of gynecological cancer: What is the future?

Cited by 9 publications

References 81 publications

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

Predicting high-risk endometrioid carcinomas using proteins

Frontline treatment of epithelial ovarian cancer

Contact Info

Product

Resources

About