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Apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in malignant transformation of salivary gland pleomorphic adenoma

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Abstract

DNA repair systems play a critical role in protecting the human genome against cumulative damage. The apurinic/apyrimidinic endonuclease 1 is a protein involved in DNA base excision repair and its expression still needs to be investigated in salivary gland tumors. The objective of this study is to analyze the immunoexpression of apurinic/apyrimidinic endonuclease 1 in pleomorphic adenomas and carcinomas ex pleomorphic adenomas of the salivary glands. A total of 33 pleomorphic adenomas and 16 carcinomas ex pleomorphic adenomas of the salivary glands underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed quantitatively. For statistical analysis, Mann–Whitney test was performed and a significance level was set at p ≤ 0.05. All analyzed tumors (n = 49) were positive for apurinic/apyrimidinic endonuclease 1. However, there was a higher median expression in carcinomas ex pleomorphic adenomas (p < 0.001). There was no difference between this protein immunoexpression and tumors of major or minor salivary gland. Overexpression was found mainly in cases of carcinomas ex pleomorphic adenomas with lymph node metastasis (p = 0.002) and invasive growth (p = 0.003), when compared to cases without metastasis and without capsular invasion (intracapsular pattern). Our findings revealed that apurinic/apyrimidinic endonuclease 1 is downregulated in pleomorphic adenomas and overexpressed in carcinomas ex pleomorphic adenomas, suggesting that this protein is possibly deregulated in pleomorphic adenoma malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior in carcinomas ex pleomorphic adenomas, which suggests that this protein may represent a prognostic biomarker in the studied salivary gland tumors.

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Acknowledgements

This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES).

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Correspondence to Leorik Pereira Silva.

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All procedures performed in this study involving the patient were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The approval of the local ethics committee is present in the methods section in this article.

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Informed consent was obtained from the patients in this study.

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Silva, L.P., Santana, T., Sedassari, B.T. et al. Apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in malignant transformation of salivary gland pleomorphic adenoma. Eur Arch Otorhinolaryngol 274, 3203–3209 (2017). https://doi.org/10.1007/s00405-017-4605-9

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  • DOI: https://doi.org/10.1007/s00405-017-4605-9

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