Research Papers: Pathology:
Strong SOD2 expression and HPV-16/18 positivity are independent events in cervical cancer
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Abstract
Silvia Helena Rabelo-Santos1, Lara Termini2, Enrique Boccardo3, Sophie Derchain4, Adhemar Longatto-Filho5,6, Maria Antonieta Andreoli7, Maria Cecília Costa2, Rafaella Almeida Lima Nunes2, Liliana Aparecida Lucci Ângelo-Andrade8, Luisa Lina Villa2,9 and Luiz Carlos Zeferino4
1School of Pharmacy, Federal University of Goiás (UFG – Universidade Federal de Goiás), Goiás, Brazil
2Innovation in Cancer Laboratory, Center of Translational Research in Oncology, Cancer Institute of São Paulo (ICESP - Instituto do Câncer do Estado de São Paulo), Faculty of Medicine of University of São Paulo (FMUSP - Faculdade de Medicina da Universidade de São Paulo), São Paulo, São Paulo, Brazil
3Laboratory of Oncovirology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo (USP - Universidade de São Paulo), São Paulo, São Paulo, Brazil
4Department of Obstetrics and Gynecololy, State University of Campinas (UNICAMP – Universidade Estadual de Campinas), Campinas, São Paulo, Brazil
5Laboratory of Medical Research, Faculty of Medicine of University of São Paulo (Faculdade de Medicina da Universidade de São Paulo-FMUSP), São Paulo, São Paulo, Brazil
6Institute of Life Sciences and Health, Faculty of Health Sciences, (ICVS), University of Minho, Braga, Portugal.
7International Research Center, A.C. Camargo Cancer Center, São Paulo, São Paulo, Brazil
8Department of Pathology, State University of Campinas (UNICAMP – Universidade Estadual de Campinas), Campinas, São Paulo, Brazil
9Department of Radiology and Oncology, Faculty of Medicine of University of São Paulo (FMUSP - Faculdade de Medicina da Universidade de São Paulo-USP), São Paulo, São Paulo, Brazil
Correspondence to:
Luiz Carlos Zeferino, email: [email protected]
Keywords: human papillomavirus; cervical intraepithelial neoplasia; squamous cell carcinoma; adenocarcinoma; superoxide dismutase-2; Pathology
Received: June 19, 2017 Accepted: March 11, 2018 Published: April 24, 2018
ABSTRACT
It is well known that persistent infection with high-risk HPV (hr-HPV), mostly HPV-16 and 18, is the main cause of cervical cancer development. Manganese superoxide dismutase (MnSOD or SOD2) are highly expressed in different neoplasia. The present study investigated SOD2 protein expression and the presence of hr-HPV types in 297 cervical samples including non-neoplastic tissue, cervical intraepithelial neoplasia grade 3 (CIN3), squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Strong SOD2 expression was significantly higher in ADC (82%) than CIN3 (52%) or SCC (64%). There was no association between SOD2 expression and HPV 16 and/or 18 detection for every lesion analyzed. Binary Logist Regression revealed that strong SOD2 expression (OR: 27.50, 6.16-122.81) and HPV 16 and/or HPV 18 (OR: 12.67, 4.04-39.74) were independently more associated with CIN3 than non-neoplastic cervix. Strong SOD2 expression (OR: 3.30, 1.23-8.86) and HPV 16 and/or HPV 18 (OR: 3.51, 1.03-11.87) were independently more associated with ADC than SCC. Similar findings for SOD2 expression were observed by the Cochran Mantel-Haenszel test, controlling for HPV-16 and/or HPV 18. In conclusion, the expression of SOD2 was increased in CIN3 and SCC, and more increased in cervical ADC than in SCC. Strong SOD2 expression was statistically independent of the presence of HPV 16 and/or 18. These findings suggest that the mitochondrial antioxidant system and HPV infection could follow independent pathways in the carcinogenesis of cervical epithelium and in the differentiation to SCC or ADC of the cervix.
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