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MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis.
Discacciati, Michelle G; Gimenes, Fabrícia; Pennacchi, Paula C; Faião-Flores, Fernanda; Zeferino, Luiz C; Derchain, Sophie M; Teixeira, Júlio C; Costa, Maria C; Zonta, Marco; Termini, Lara; Boccardo, Enrique; Longatto-Filho, Adhemar; Consolaro, Marcia E L; Villa, Luisa L; Maria-Engler, Silvya S.
Afiliación
  • Discacciati MG; Laboratory of Clinical Cytopathology, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, Brazil.
  • Gimenes F; Clinical Cytology Laboratory, State University of Maringá (UEM), Maringá, Paraná, Brazil.
  • Pennacchi PC; Laboratory of Clinical Cytopathology, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, Brazil.
  • Faião-Flores F; Laboratory of Clinical Cytopathology, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, Brazil.
  • Zeferino LC; Department of Obstetrics and Gynecology, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
  • Derchain SM; Department of Obstetrics and Gynecology, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
  • Teixeira JC; Department of Obstetrics and Gynecology, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
  • Costa MC; School of Medicine, Santa Casa de São Paulo, INCT-HPV at Santa Casa Research Institute, São Paulo, Brazil.
  • Zonta M; LEMC Laboratory, Discipline of Infectology, UNIFESP; and Department of Pathology, Santo Amaro University, São Paulo, Brazil.
  • Termini L; School of Medicine, Santa Casa de São Paulo, INCT-HPV at Santa Casa Research Institute, São Paulo, Brazil.
  • Boccardo E; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Longatto-Filho A; Laboratory of Medical Investigation (LIM), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil. Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal. ICVS/3B's-PT Government Associate Laboratory, Braga/Guimar
  • Consolaro ME; Clinical Cytology Laboratory, State University of Maringá (UEM), Maringá, Paraná, Brazil.
  • Villa LL; School of Medicine, Santa Casa de São Paulo, INCT-HPV at Santa Casa Research Institute, São Paulo, Brazil. Department of Radiology and Oncology, School of Medicine, University of São Paulo, São Paulo, Brazil.
  • Maria-Engler SS; Laboratory of Clinical Cytopathology, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, Brazil. silvya@usp.br.
Cancer Epidemiol Biomarkers Prev ; 24(10): 1539-47, 2015 Oct.
Article en En | MEDLINE | ID: mdl-26261088
BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Chlamydia / Regulación Neoplásica de la Expresión Génica / Cervicitis Uterina / Neoplasias del Cuello Uterino / Metaloproteinasa 9 de la Matriz / Infecciones por Papillomavirus / Proteínas Ligadas a GPI Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Asunto de la revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Año: 2015 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Chlamydia / Regulación Neoplásica de la Expresión Génica / Cervicitis Uterina / Neoplasias del Cuello Uterino / Metaloproteinasa 9 de la Matriz / Infecciones por Papillomavirus / Proteínas Ligadas a GPI Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Asunto de la revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Año: 2015 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos