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Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer.

ABSTRACT: New therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03-24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06-20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16-223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.

SUBMITTER: Bastiaansen AEM

PROVIDER: S-EPMC7749122 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer.

Bastiaansen Anna E M AEM Timmermans A Mieke AM Smid Marcel M van Deurzen Carolien H M CHM Hulsenboom Esther S P ESP Prager-van der Smissen Wendy J C WJC Foekens Renée R Trapman-Jansen Anita M A C AMAC Sillevis Smitt Peter A E PAE Luider Theo M TM Martens John W M JWM vanDuijn Martijn M MM

Scientific reports 20201218 1

New therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mG ...[more]

PMID: 33339858

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Project description:BackgroundAnti-Androgen Receptor (AR) therapy holds promise for a subset of AR expressing triple-negative breast cancer (TNBC) patients. However, current AR assays are suboptimal in detecting the dynamic range of AR expression, contributing to its controversial role in TNBC disease prognosis. This study is aimed at evaluating the feasibility of qRT-PCR to sensitively and robustly detect AR mRNA levels for prognostication.MethodsmRNA expression profiling was performed on FFPE blocks from a retrospective cohort of 101 TNBC patients using qRT-PCR and compared with AR protein expression by immunohistochemistry . Statistical analyses included Spearman's rank correlation, Chi-square and Kaplan-Meier analyses. Distant Metastasis Free Survival was used as the end point in survival analysis.ResultsAR mRNA expression was observed in 34/101 patients (34%) whereas 12/80 cases (15%) were positive by IHC. qRT-PCR could thus detect more AR positive patients as compared to IHC, with 75% (9/12) concordance between the two methods. Co-expression of GATA3 and FOXA1 mRNA was observed in 85 and 88% of AR mRNA positive tumors, respectively. AR mRNA positivity was significantly correlated with age at disease onset (p = 0.02), high FOXA1/GATA3 (p < 0.05) and distant recurrence. AR mRNA positive patients had poorer DMFS (43%; p = 0.002). DMFS dropped further to 26% (p = 0.006) in AR (+)/high FOXA1/GATA3 patients. AR mRNA expression together with node positivity had the worst DMFS (23%; p < 0.0001) compared to patients who were either positive for any one of these, or negative for both AR and node status. Low Ki67 mRNA with AR mRNA positivity also had poorer DMFS (39%; p = 0.001) compared to patients expressing low Ki67 with no AR mRNA expression.ConclusionqRT-PCR was more sensitive and reliable in detecting the dynamic expression levels of AR compared to IHC and this variation could be explained by the higher sensitivity of the former method. High AR mRNA expression was strongly associated with expression of AR protein, high FOXA1/GATA3 mRNA, and with poor prognosis. qRT-PCR was more efficient in detecting the AR positive cases compared to IHC. A distinct signature involving high GATA3/FOXA1, low Ki67, and node positivity in AR mRNA positive tumors correlated with poor prognosis. Thus, AR mRNA screening can serve as an effective prognostic marker along with offering potential targeted therapy options for TNBC.

Dataset Information

Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer.

Publications

Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer.

Similar Datasets

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