Estrogen receptor \u03b2 is associated with expression of cancer associated genes and survival in ovarian cancer

Susanne Schüler-Toprak,Florian Weber,Oliver Treeck,Olaf Ortmann,Maciej Skrzypczak

doi:10.1186/s12885-018-4898-0

Susanne Schüler-Toprak, Florian Weber + Show 3 more

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https://doi.org/10.1186/s12885-018-4898-0

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Abstract

BackgroundIn ovarian cancer, the role of estrogen receptors (ERs), particularly of ERβ, being suggested as tumor suppressor in breast and prostate cancer, remains unclear. We examined the expression of nuclear and cytoplasmic ERβ in ovarian cancer and correlated it with expression of ovarian cancer markers CA125, CEA and CA72–4, steroid hormone receptors ERα and PR, cancer-associated genes EGFR, p53, HER2 and proliferation marker Ki-67. Additionally we examined to what extent expression of ERβ and the other proteins affects survival of ovarian cancer patients.MethodsWe established a tissue microarray from 171 ovarian cancer patients and performed immunohistochemical analyses of the mentioned proteins.ResultsNuclear ERβ was detected in 47.31% of the ovarian cancer tissues and cytoplasmic expression of this receptor was observed in 23.08%. Nuclear expression of ERβ was significantly decreased in the G3 subgroup compared to better differentiated cancers (p < 0.01) and correlated with ovarian cancer markers CEA (95% CI 0.1598–0.4465; p < 0.0001) and CA72–4 (95% CI 0.05953–0.3616; p < 0.01). Cytoplasmic ERβ expression correlated with EGFR levels (95% CI 0.1059–0.4049; p < 0.001). ERα expression was associated with expression of CA125 and PR. Overall survival of patients with tumors expressing cytoplasmic ERβ was significant longer compared to those with ERβ-negative ovarian cancer (chi-square statistic of the log-rank, p < 0.05). Progression-free survival was dependent on expression of PR (chi-square statistic of the log-rank, p < 0.05) and Ki-67 (p = 0.05).ConclusionsOur data suggest an important, but distinct role of nuclear and cytoplasmic ERβ expression in ovarian cancer and encourage further studies on its role in this cancer entity.

Highlights

In ovarian cancer, the role of estrogen receptors (ERs), of ERβ, being suggested as tumor suppressor in breast and prostate cancer, remains unclear
The histopathological characteristics of the patients are shown in Table 1. 63.7% of the tumors were diagnosed in FIGO (International Federation of Gynaecologists and Obstetricians) stages III and IV (38.6 and 25.15, respectively)
Expression of steroid hormone receptors in ovarian cancer tissue Nuclear ERβ was expressed in 47.31%, and cytoplasmic expression of this receptor was detected in 23.08% of ovarian cancer specimens (Fig. 1, Table 2)

Summary

Introduction

The role of estrogen receptors (ERs), of ERβ, being suggested as tumor suppressor in breast and prostate cancer, remains unclear. We examined to what extent expression of ERβ and the other proteins affects survival of ovarian cancer patients. Previous studies clearly suggest a tumor suppressive role of ERβ in ovarian cancer as it has been shown for breast or prostate cancer [9,10,11]. Our Schüler-Toprak et al BMC Cancer (2018) 18:981 results from a phenotype-genotype association study suggested that the single nucleotide polymorphism rs3020449 in the promoter region of ESR2 gene might affect progression of ovarian cancer [14]

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