Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

Cinzia Borgogna, Simone Lanfredini, Alberto Peretti, Marco De Andrea, Elisa Zavattaro, Enrico Colombo, Marco Quaglia, Renzo Boldorini, Umberto Miglio, John Doorbar, Jan N Bouwes Bavinck, Koen D. Quint, Maurits Nc De Koning, Santo Landolfo, Marisa Gariglio

Research output: Contribution to journalArticle

Abstract

The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.

Original languageEnglish
Pages (from-to)1101-1115
Number of pages15
JournalModern Pathology
Volume27
Issue number8
DOIs
Publication statusPublished - 2014

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Keywords

  • -HPV
  • immunosuppression
  • kidney transplant recipients
  • skin cancer
  • viral life cycle
  • β

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Borgogna, C., Lanfredini, S., Peretti, A., De Andrea, M., Zavattaro, E., Colombo, E., Quaglia, M., Boldorini, R., Miglio, U., Doorbar, J., Bavinck, J. N. B., Quint, K. D., De Koning, M. N., Landolfo, S., & Gariglio, M. (2014). Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients. Modern Pathology, 27(8), 1101-1115. https://doi.org/10.1038/modpathol.2013.240