Loss of ZNF516 protein expression is related with HR-HPV infection and cervical preneoplastic lesions

  • Carmen Ili
  • Jaime Lopez
  • Kurt Buchegger
  • Ismael Riquelme
  • Javier Retamal
  • Louise Zanella
  • Barbara Mora-Lagos
  • Carolina Vivallo
  • Juan C. Roa
  • Priscilla BrebiEmail author
Gynecologic Oncology



Cervical cancer is an important health issue among women worldwide. Cervical smear and human papillomavirus detection are the most used screening methods to detect preneoplastic and neoplastic lesions. However, as neither can predict cervical development, new markers are needed for this disease. ZNF516, a potential tumor suppressor gene, has been found altered in cervical cancer. The objective of this study was to determine ZNF516 immunohistochemistry frequency in cervical biopsies and its association with clinicopathological parameters, to evaluate its potential as marker in cervical lesions.


A retrospective series of 452 formalin-fixed, paraffin-embedded (FFPE) cervical biopsies, obtained between 2002 and 2007, were selected for immunohistochemistry of ZNF516, p16 and Ki-67 markers. Human papillomavirus genotyping was performed on 272 of these samples through reverse line blot assay.


An inverse relation between ZNF516 expression and cervical lesions grade (P < 0.001) was observed, given this protein was found mainly expressed in normal tissues, while was decreased in cervical lesions. As expected, the proliferation markers p16 and Ki-67 were found highly expressed in cervical cancer compared to normal tissues, and inversely correlated to ZNF516 expression (P < 0.01). High oncogenic risk-Human papillomavirus presence also was related to the lack of ZNF516 expression in cervical lesions (P < 0.05), and the detection of these two parameters showed a high sensitivity (70.9%) for preneoplastic lesions detection.


The loss of ZNF516 expression was found in cervical lesions, and its detection potentially could be used as a complementary marker of early diagnosis in cervical lesions.


ZNF516 Cervical cancer Immunohistochemistry p16 Ki-67 Human papillomavirus 



Fondo Nacional de Desarrollo Científico y Tecnológico de Chile (FONDECYT) nos. 3130630, 11150622, 11150802, 3180550 and 3170826; Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias no. 15130011; The Millennium Institute on Immunology and Immunotherapy no. P09-016-F.

Author contributions

Protocol/project development, data collection or management, data analysis and manuscript writing/editing. CI: project development, data management, data analysis and Manuscript writing. JL: protocol development, data collection and manuscript editing. KB: data analysis and manuscript editing. IR: data analysis and manuscript editing. JR: data collection and manuscript editing. LZ: data analysis and manuscript editing. BM: data collection and manuscript editing. CV: data collection and manuscript editing. JCR: data collection and management and manuscript. PB: project development, data management, data analysis and manuscript writing editing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants 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. This research is a retrospective study including biopsy tissue samples of archive. Therefore, for this type of study formal consent is not required. The use of these samples was approved by the ethical scientific committee of School of Medicine (Document no. 17/012), Universidad de La Frontera, Temuco, Chile.

Informed consent

This research is a retrospective study including biopsy tissue samples of archive. Therefore, for this study informed consent was not obtained. The use of these samples was approved by the ethical scientific committee of School of Medicine (Document no. 17/012), Universidad de La Frontera, Temuco, Chile.

Supplementary material

404_2018_5012_MOESM1_ESM.docx (20 kb)
Supplementary file1 (DOCX 20 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratorio de Patología Molecular, Centro de Excelencia en Medicina Traslacional-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN)Universidad de La FronteraTemucoChile
  2. 2.Instituto de Ciencias Biomédicas, Facultad de Ciencias de La SaludUniversidad Autónoma de ChileTemucoChile
  3. 3.Departamento Anatomía Patológica, Facultad de MedicinaUniversidad de La FronteraTemucoChile
  4. 4.Unidad de Anatomía Patológica, Hospital Hernán Henríquez AravenaTemucoChile
  5. 5.Departamento de Ciencias Preclínicas, Facultad de MedicinaUniversidad de La FronteraTemucoChile
  6. 6.Department of Pathology, UC Centre for Investigational Oncology (CITO), Advanced Centre for Chronic Diseases (ACCDis), The Millennium Institute On Immunology and ImmunotherapyPontificia Universidad Católica de ChileSantiagoChile

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