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

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.

• Authors: 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 N C de Koning, Santo Landolfo, Marisa Gariglio
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 27 Issue 8 Pg. 1101-15 (Aug 2014) ISSN: 1530-0285 [Electronic] United States
• PMID: 24390217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Capsid Proteins
• DNA, Viral
• HPV L1 protein, Human papillomavirus
• Oncogene Proteins, Viral
• MCM7 protein, human
• Minichromosome Maintenance Complex Component 7

Topics

• Aged
• Betapapillomavirus (chemistry, genetics, growth & development, isolation & purification)
• Biomarkers, Tumor (analysis)
• Capsid Proteins (analysis)
• Carcinoma, Basal Cell (chemistry, pathology, virology)
• Carcinoma, Squamous Cell (chemistry, pathology, virology)
• DNA, Viral (isolation & purification)
• Female
• Hospitals, University
• Human Papillomavirus DNA Tests
• Humans
• Immunohistochemistry
• Italy
• Keratosis, Actinic (metabolism, pathology, virology)
• Kidney Transplantation (adverse effects)
• Male
• Middle Aged
• Minichromosome Maintenance Complex Component 7 (analysis)
• Oncogene Proteins, Viral (analysis)
• Papillomavirus Infections (pathology, virology)
• Polymerase Chain Reaction
• Predictive Value of Tests
• Risk Factors
• Skin Neoplasms (chemistry, pathology, virology)
• Virus Replication