Quantification of ER/PR expression in ovarian low-grade serous carcinoma

Escobar, Jorge; Klimowicz, Alexander C.; Dean, Michelle L.; Chu, Pamela; Nation, Jill; Nelson, Gregg; Ghatage, Prafull; Kalloger, Steve E.; Köbel, Martin

doi:10.1016/j.ygyno.2012.10.013

Cited by 71 publications

(48 citation statements)

References 34 publications

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“…PGR was selected for validation. It is expressed in most SBT (37) and in approximately 30% of serous EOC (38) and had the largest fold change in comparing paired samples. Consistent with expression array results, immunohistochemistry of progesterone receptor A and B (PRA and PRB) in 10 FFPE samples of SBT-EOC revealed strong differential expression in SBT versus invasive regions for both progesterone receptor isoforms (Fig.…”

Section: Nras Mutations Are Confined To Invasive Cancersmentioning

confidence: 99%

Genomic Classification of Serous Ovarian Cancer with Adjacent Borderline Differentiates RAS Pathway and TP53-Mutant Tumors and Identifies NRAS as an Oncogenic Driver

Emmanuel

Chiew

George

et al. 2014

Clinical Cancer Research

111

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Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinumbased chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies.Experimental Design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling.Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC.Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. Clin Cancer Res; 20(24); 6618-30. Ó2014 AACR.

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Section: Nras Mutations Are Confined To Invasive Cancersmentioning

confidence: 99%

Genomic Classification of Serous Ovarian Cancer with Adjacent Borderline Differentiates RAS Pathway and TP53-Mutant Tumors and Identifies NRAS as an Oncogenic Driver

Emmanuel

Chiew

George

et al. 2014

Clinical Cancer Research

111

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“…Generally, the incidence of ovarian cancer starts to elevate in the peri-menopausal period, a time in which circulating estrogen levels tend to rise relative to the earlier reproductive stages, as shown in recent meta-analysis of observational data [6]. HGSOC, the most common histologic subtype of ovarian cancer and known to have aggressive tumor biology, expresses estrogen receptor in 60-85% of the samples [7,8]. Estrogen replacement therapy has been related to increased ovarian cancer incidence and mortality related to disease [9][10][11][12].…”

Section: Introductionmentioning

confidence: 98%

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Matsuo

Todd

Yoshino

et al. 2013

Gynecologic Oncology

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Objective-Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma.Methods-Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes.Results-LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), Conclusion-Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.

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“…Previous studies have shown considerable estrogen receptor (ER) and progesterone receptor (PR) expression levels in LGSC [13, 14], and hormone therapy might be a promising alternative for recurrent LGSC [15]. However, the expression levels of other hormone receptors related to the hypothalamic-pituitary-gonadal axis (androgen receptor (AR), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and gonadotropin-releasing receptor (GnRHR)) in LGSC, which could also mediate the effects of steroid hormones on the development and progression of ovarian cancer, have not been shown.…”

Section: Introductionmentioning

confidence: 99%

Expression of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC)

Feng

Wen

et al. 2017

J Ovarian Res

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BackgroundThe aim of our study was to investigate the clinical features and expression levels of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC).MethodsWe retrospectively investigated the clinical features of 26 consecutive patients with LGSC who underwent primary staging or debulking surgery between April 2005 and June 2013 in our center; concomitant primary high-grade serous ovarian cancer (HGSC) patients were randomly selected at a 2:1 ratio for comparison. Tissue microarrays were constructed from the LGSC and HGSC specimens, and the expression levels of six hormone receptors in the hypothalamic pituitary-gonadal axis were analyzed by immunohistochemistry.ResultsThe median (range) age of patients with LGSC was 54 (27–77) years. According to the FIGO staging system, the cases were distributed as follows: stage I, 6 (23.1%); stage II, 0 (0%); stage III, 19 (73.1%); and stage IV, 1 (3.8%). The 2-year and 5-year overall survival rates for LGSC were 91.8% and 67.5%, respectively. The expression levels of the hormone receptors were as follows: ER, 80.8%; PR, 34.6%; AR, 53.8%; FSHR, 84.0%; LHR, 65.4%; and GnRHR, 100%. Hormone receptor-positive patients had a better prognosis compared with hormone receptor-negative patients, but the difference was not significant.ConclusionsOur study presented a higher overall survival rate and distinctive hormone receptor expression levels of LGSC patients compared with the HGSC cohort. Patients with positive hormone receptor expression tended to have a better prognosis than the corresponding hormone receptor negative patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-016-0300-5) contains supplementary material, which is available to authorized users.

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Quantification of ER/PR expression in ovarian low-grade serous carcinoma

Cited by 71 publications

References 34 publications

Genomic Classification of Serous Ovarian Cancer with Adjacent Borderline Differentiates RAS Pathway and TP53-Mutant Tumors and Identifies NRAS as an Oncogenic Driver

Genomic Classification of Serous Ovarian Cancer with Adjacent Borderline Differentiates RAS Pathway and TP53-Mutant Tumors and Identifies NRAS as an Oncogenic Driver

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Expression of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC)

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