Oncotarget

Research Papers: Pathology:

Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium

Carla Bartosch _, Sara Monteiro-Reis, Diogo Almeida-Rios, Renata Vieira, Armando Castro, Manuel Moutinho, Marta Rodrigues, Inês Graça, José Manuel Lopes and Carmen Jerónimo

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Oncotarget. 2016; 7:1144-1154. https://doi.org/10.18632/oncotarget.6691

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Abstract

Carla Bartosch1,2,3, Sara Monteiro-Reis1,2, Diogo Almeida-Rios1,2, Renata Vieira1, Armando Castro4, Manuel Moutinho4, Marta Rodrigues4, Inês Graça2, José Manuel Lopes3,4,5,* and Carmen Jerónimo2,6,*

1 Department of Pathology, Portuguese Oncology Institute-Porto (IPO-Porto), Porto, Portugal

2 Cancer Epigenetics & Biology Group, Research Center, Portuguese Oncology Institute-Porto, Porto, Portugal

3 Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal

4 Department of Pathology, Centro Hospitalar São João (CHSJ), Porto, Portugal

5 IPATIMUP (Institute of Molecular Pathology and Immunology, University of Porto), Porto, Portugal

6 Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

* These authors are Joint senior authors

Correspondence to:

Carla Bartosch, email:

Keywords: endometrial carcinoma, endometrium, sirtuin, SIRT1, SIRT7, Pathology Section

Received: June 21, 2015 Accepted: December 08, 2015 Published: December 19, 2015

Abstract

Sirtuins participate in hormone imbalance, metabolism and aging, which are important processes for endometrial cancer (EC) development. Sirtuins mRNA expression (SIRT1 to 7) was determined in 76 ECs (63 Type I, 12 Type II and one mixed EC), and 30 non-neoplastic endometria (NNE) by quantitative real-time PCR. SIRT1 and SIRT7 protein expression was evaluated by immunohistochemistry using Allred score. Compared to NNE, ECs showed SIRT7 (p < 0.001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed. No significant differences were observed for SIRT3 and SIRT6. Type II ECs displayed lower SIRT1 (p = 0.032) and SIRT3 (p = 0.016) transcript levels than Type I ECs. Concerning protein expression, SIRT1 immunostaining median score was higher in ECs compared to NNE epithelium (EC = 5 vs. NNE = 2, p < 0.001), while SIRT7 was lower in ECs (EC = 6 vs. NNE = 7, p < 0.001). No significant associations were found between SIRT1/7 immunoexpression and histological subtype, grade, lymphovascular invasion or stage. Our data shows that sirtuins are deregulated in EC. The diversity of expression patterns observed suggests that sirtuins may have distinctive roles in endometrial cancer similarly to what has been described in other cancer models.


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