Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma

Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and imp...

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Autores principales:	Christian Doll, Carolin Bestendonk, Kilian Kreutzer, Konrad Neumann, Anne Pohrt, Irena Trzpis, Steffen Koerdt, Steffen Dommerich, Max Heiland, Jan-Dirk Raguse, Korinna Jöhrens
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oral squamous cell carcinoma estrogen receptor alpha survival prognosis hormone receptor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9dd71a0afe89485aba8b154eef29020b
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spelling	oai:doaj.org-article:9dd71a0afe89485aba8b154eef29020b2021-11-25T17:03:41ZPrognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma10.3390/cancers132257632072-6694https://doaj.org/article/9dd71a0afe89485aba8b154eef29020b2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5763https://doaj.org/toc/2072-6694Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (<i>n</i> = 11; 11/302) or lymph node metastases (<i>n</i> = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (<i>p =</i> 0.012; <i>p</i> = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: <i>p</i> = 0.0013; <i>p</i> < 0.0001; females: <i>p</i> = 0.56; <i>p</i> = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: <i>p</i> < 0.0001; <i>p</i> < 0.0001; females: <i>p</i> = 0.95; <i>p</i> = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; <i>p</i> = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; <i>p</i> < 0.001) in the male cohort. There was a significant difference (<i>p</i> = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (<i>p</i> = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (<i>p</i> = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.Christian DollCarolin BestendonkKilian KreutzerKonrad NeumannAnne PohrtIrena TrzpisSteffen KoerdtSteffen DommerichMax HeilandJan-Dirk RaguseKorinna JöhrensMDPI AGarticleoral squamous cell carcinomaestrogen receptor alphasurvivalprognosishormone receptorNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5763, p 5763 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral squamous cell carcinoma estrogen receptor alpha survival prognosis hormone receptor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	oral squamous cell carcinoma estrogen receptor alpha survival prognosis hormone receptor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Christian Doll Carolin Bestendonk Kilian Kreutzer Konrad Neumann Anne Pohrt Irena Trzpis Steffen Koerdt Steffen Dommerich Max Heiland Jan-Dirk Raguse Korinna Jöhrens Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma
description	Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (<i>n</i> = 11; 11/302) or lymph node metastases (<i>n</i> = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (<i>p =</i> 0.012; <i>p</i> = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: <i>p</i> = 0.0013; <i>p</i> < 0.0001; females: <i>p</i> = 0.56; <i>p</i> = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: <i>p</i> < 0.0001; <i>p</i> < 0.0001; females: <i>p</i> = 0.95; <i>p</i> = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; <i>p</i> = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; <i>p</i> < 0.001) in the male cohort. There was a significant difference (<i>p</i> = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (<i>p</i> = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (<i>p</i> = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.
format	article
author	Christian Doll Carolin Bestendonk Kilian Kreutzer Konrad Neumann Anne Pohrt Irena Trzpis Steffen Koerdt Steffen Dommerich Max Heiland Jan-Dirk Raguse Korinna Jöhrens
author_facet	Christian Doll Carolin Bestendonk Kilian Kreutzer Konrad Neumann Anne Pohrt Irena Trzpis Steffen Koerdt Steffen Dommerich Max Heiland Jan-Dirk Raguse Korinna Jöhrens
author_sort	Christian Doll
title	Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma
title_short	Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma
title_full	Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma
title_fullStr	Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma
title_full_unstemmed	Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma
title_sort	prognostic significance of estrogen receptor alpha in oral squamous cell carcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9dd71a0afe89485aba8b154eef29020b
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Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma

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