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. 2017 Feb 27;18(3):515.
doi: 10.3390/ijms18030515.

Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications

Peter Rambau  1   2 , Linda E Kelemen  3   4 , Helen Steed  5 , May Lynn Quan  6 , Prafull Ghatage  7 , Martin Köbel  8
Affiliations

Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications

Peter Rambau et al. Int J Mol Sci. .

Abstract

This paper aims to validate whether hormone receptor expression is associated with longer survival among women diagnosed with ovarian endometrioid carcinoma (EC), and whether it identifies patients with stage IC/II tumors with excellent outcome that could be spared from toxic chemotherapy. Expression of estrogen receptor (ER) and progesterone receptor (PR) was assessed on 182 EC samples represented on tissue microarrays using the Alberta Ovarian Tumor Type (AOVT) cohort. Statistical analyses were performed to test for associations with ovarian cancer specific survival. ER or PR expression was present in 87.3% and 86.7% of cases, respectively, with co-expression present in 83.0%. Expression of each of the hormonal receptors was significantly higher in low-grade tumors and tumors with squamous differentiation. Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08-0.42, p = 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10-0.53, p = 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease. However, the five-year ovarian cancer specific survival among women with ER positive stage IC/II EC was 89.0% (standard error 3.3%) and for PR positive tumors 89.9% (standard error 3.2%), robustly below the 95% threshold where adjuvant therapy could be avoided. We validated the association of hormone receptor expression with ovarian cancer specific survival independent of standard predictors in an independent sample set of EC. The high ER/PR co-expression frequency and the survival difference support further testing of the efficacy of hormonal therapy in hormone receptor-positive ovarian EC. The clinical utility to identify a group of women diagnosed with EC at stage IC/II that could be spared from adjuvant therapy is limited.

Keywords: endometrioid; estrogen receptor; hormonal therapy; ovarian cancer; progesterone receptor; prognosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier curves of ovarian cancer specific survival for endometrioid carcinoma by hormone receptor status. (A) Survival by estrogen receptor (ER) (log rank p = 0.0005) red line and red framed image: diffuse ER expression; orange line and orange framed image: focal ER expression, blue line and blue framed image: absence of ER expression in tumor epithelium (note positive intrinsic control); (B) Survival by progesterone receptor (PR) (log rank p = 0.0003) red line and red framed image: diffuse PR expression (note absence of PR expression in areas of squamous differentiation); orange line and orange framed image: focal PR expression, blue line and blue framed image: absence of PR expression in tumor epithelium (note positive intrinsic control).
Figure 2
Figure 2
Patients with stage IC/II tumors: association between ER expression and benefit from adjuvant chemotherapy. (A) Survival of women diagnosed with ovarian endometrioid carcinoma stage IC/II who did (n = 76, blue line) or did not receive adjuvant chemotherapy (n = 27, red line), log rank p = 0.32; (B) Survival of women diagnosed with ovarian endometrioid carcinoma stage IC/II with ER negative tumors who did (n = 10, blue line) or did not receive adjuvant chemotherapy (n = 3, red line), log rank p = 0.19; (C) Survival of women diagnosed with ovarian endometrioid carcinoma stage IC/II with ER negative tumors who did (n = 66, blue line) or did not receive adjuvant chemotherapy (n = 24, red line), log rank p = 0.76.
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