APOBEC3A Expression in Penile Squamous Cell Carcinoma

Pathobiology. 2018;85(3):169-178. doi: 10.1159/000479007. Epub 2017 Nov 23.


Background: APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are cytidine deaminases that have been implicated in the host defense against viruses by blocking viral replication. They have also been shown to play a role in genome hypermutation in several human cancers. An APOBEC3 hypermutation signature has been discovered in cervical cancer, which is intimately associated with infection by high-risk human papillomaviruses (HPVs). At the same time, HPV genomes themselves are subject to DNA editing by APOBECs. Similar to cervical cancer, a proportion of penile squamous cell carcinomas (SCCs) is etiologically driven by high-risk HPVs, but very little is known about the role of APOBECs in penile SCC development and progression.

Methods: A series of 34 penile SCCs was analyzed for the expression of APOBEC3A protein by immunohistochemistry. HPV genotyping was carried out using a bead-based multiplex hybridization assay preceded by BSGP5+6+ primer-based amplification.

Results: We found a frequent reduction of APOBEC3A protein expression in the invasive parts of the majority of HPV-negative penile SCCs. In contrast, the majority of HPV-positive penile SCCs retained APOBEC3A expression during malignant progression.

Conclusion: Our results suggest that APOBEC3A expression is downregulated during progression towards invasiveness in HPV-negative penile SCC, but maintained in HPV-positive penile SCC. How high-risk HPV-infected tumor cells tolerate high APOBEC3A, which appears to exert tumor suppressive functions in HPV-negative penile SCCs, remains to be elucidated.

Keywords: APOBECs; Human papillomaviruses; Penile squamous cell carcinomas.

MeSH terms

  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / metabolism*
  • Cohort Studies
  • Cytidine Deaminase / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Germany
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • Penile Neoplasms / complications
  • Penile Neoplasms / metabolism*
  • Proteins / metabolism*
  • Retrospective Studies


  • Proteins
  • APOBEC3A protein, human
  • Cytidine Deaminase