Abstract | BACKGROUND: OBJECTIVE: Classification of penile lesions into HPV-induced or HPV-negative via immunohistochemical demonstration of p16(ink4a) overexpression, a surrogate marker for transforming HPV-high-risk infections, and p53 expression in the absence of p16(ink4a) overexpression. METHODS: Archival formalin-fixed material of 123 invasive penile cancers and 43 pre-invasive lesions was evaluated for the presence of LS, LP, 28 HPV genotypes, and expression of p53 and p16(ink4a). RESULTS: Seventy-two of 123 SCCs and 33 of 43 pre-invasive lesions showed p16(ink4a) overexpression independent of HPV-HR genotypes involved; 66 of 72 SCCs and 29 of 43 precursor lesions revealed a single HPV-high-risk-genotype (HPV-HR16 in 76% followed by HPV33, HPV31, HPV45, HPV18, HPV56); 5 of 72 SCCs and 4 of 43 precursor lesions revealed multiple HPV-HR-genotypes. One SCC revealed HPV-LR and HR- DNA. Fifty-one of 123 SCCs and 10 precursor lesions were p16(ink4a) negative, but showed nuclear p53 expression in tumor cells and basal keratinocytes. Forty-nine of 51 SCCs and 10 of 10 precursor lesions lacked HPV DNA. Two of 51 SCCs contained HPV18 and HPV45 DNA, respectively, but p16(ink4a) negativity classified them as non-HPV-induced. Twenty-seven of 51 SCCs showed peritumoral LS, 13 of 51 SCCs showed peritumoral LP, and 11 SCCs revealed no peritumoral tissue. Histologically, HPV-negative precursors showed hyperkeratotic, verrucous, atrophic, and basaloid differentiation. LIMITATIONS: This was a retrospective study. CONCLUSIONS:
p16(ink4a) overexpression identifies HPV-HR-induced penile carcinogenesis independent of HPV-HR genotype. p53 expression along with p16(ink4a) negativity identifies HPV-negative cancers. Correct etiologic classification of penile lesions during diagnostic work-up allows optimal therapy decisions.
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Authors | Sebastian Mannweiler, Stephan Sygulla, Elke Winter, Sigrid Regauer |
Journal | Journal of the American Academy of Dermatology
(J Am Acad Dermatol)
Vol. 69
Issue 1
Pg. 73-81
(Jul 2013)
ISSN: 1097-6787 [Electronic] United States |
PMID | 23474228
(Publication Type: Journal Article)
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Copyright | Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Cyclin-Dependent Kinase Inhibitor p16
- Tumor Suppressor Protein p53
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Topics |
- Alphapapillomavirus
- Carcinoma, Squamous Cell
(metabolism)
- Cyclin-Dependent Kinase Inhibitor p16
(metabolism)
- Gene Expression Regulation, Neoplastic
(physiology)
- Genotype
- Humans
- Immunohistochemistry
- Male
- Papillomavirus Infections
(complications)
- Penile Neoplasms
(classification, metabolism, virology)
- Retrospective Studies
- Tumor Suppressor Protein p53
(metabolism)
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