Sirtuin1 expression and survival in endometrial and clear-cell uterine cancer

Susanne Beyer,Sarah Meister,Artur Mayerhofer,Elisa Schmöckel,Thomas Kolben,Fabian Trillsch,Theresa M Kolben,Fangfang Chen,Doris Mayr,Sven Mahner,Bastian Czogalla,Alexander Burges,Anna Hester,Udo Jeschke

doi:10.1007/s00418-020-01873-x

Susanne Beyer, Sarah Meister + Show 12 more

Open Access

https://doi.org/10.1007/s00418-020-01873-x

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Abstract

Several risk factors like obesity and hyperlipidemia were described for endometrial cancer. Here, the nuclear NAD-dependent histone-deacetylase Sirtuin1 (SIRT1) seems to be important. SIRT1 is also involved in cell regulatory mechanisms and can serve as tumor promotor or suppressor. Its role in tumor biology is not clear yet. In this study, we evaluated and correlated the SIRT1 expression with patients’ tumor characteristics in endometrioid and clear-cell cancer of the uterus. 65 paraffin-embedded samples of patients with endometrial and clear-cell cancer of the uterus were immunohistochemically stained and SIRT1 expression was evaluated by immunoreactive score. The results were correlated to clinical and pathological tumor characteristics as well as to the expression of ARID1A and β-Catenin. The staining was significantly more intensive in uterine endometrioid carcinoma compared to uterine clear-cell carcinoma (p = 0.007). The expression of SIRT1 correlated significantly with the membranous expression of β-Catenin (p = 0.028) and ARID1A (p = 0.021). Patients with positive Sirtuin1 expression had a significantly better progression-free survival (p = 0.042), the overall survival showed a trend towards a better prognosis (p = 0.070). SIRT1 expression seems to be associated with improved progression-free survival in uterine cancer (endometrioid and clear-cell) and is correlated to the tumor suppressors β-Catenin and ARID1A. Further studies are necessary to elucidate the role of SIRT1 in uterine and ovarian cancer and its potential as a therapeutic target.

Highlights

Endometrial cancer is the most common gynecologic cancer in developed countries (Siegel et al 2018)
Endometrial cancer is classified into type-I and type-II cancers (Kurman RJ 2014)
Many studies exist observing the prognostic value of different epigenetic changes in uterine cancers, but less is known about the role of SIRT1 in these cancer types

Summary

Introduction

Endometrial cancer is the most common gynecologic cancer in developed countries (Siegel et al 2018). The incidence in Germany is 11,700 (new diseases per year), which makes it the fourth common cancer among women in Germany [Robert Koch-Institut (Hrsg.) (2010)]. Several risk factors like obesity, hyperlipidemia, infertility or late onset of the menopause were described (Ali 2014; Bokhman 1983). Another risk factor seems to be the history of endometriosis (Zucchetto et al 2009). Like ARID1A and β-Catenin are common in endometriosis and associated cancers, where they can act as tumor suppressors (Wiegand et al 2010)

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