Response to interferon treatment decreases with epidermal dedifferentiation in condylomas

• Published in: Antiviral research Vol. 32; no. 1; pp. 19 - 26
• Main Authors: Arany, Istvan, Brysk, Miriam M., Brysk, Henry, Tyring, Stephen K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.1996; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Base Sequence; Biological and medical sciences; Biomarkers; Cell Differentiation - genetics; Condyloma; Condylomata Acuminata - pathology; Condylomata Acuminata - therapy; Condylomata Acuminata - virology; DNA Primers - genetics; Epidermal differentiation; Gene expression; Gene Expression Regulation, Viral; Genes, Viral; Human papillomavirus; Humans; Interferon treatment; Interferons - therapeutic use; Keratins - genetics; Medical sciences; Papillomaviridae - genetics; Pharmacology. Drug treatments; Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Viral - genetics; RNA, Viral - metabolism; Skin Diseases, Viral - pathology; Skin Diseases, Viral - therapy; Skin Diseases, Viral - virology; Human papillomavirus; Epidermal differentiation; Gene expression; Interferon treatment; Condyloma; Human; Treatment efficiency; Cytokine; Keratinization; Epidermis; Histology; Papovaviridae; Cell differentiation; Genital diseases; Infection; Papillomavirus; Virus; Chemotherapy; Sexually transmitted disease; Viral disease; Antiviral; Condyloma acuminatum; Interferon
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/0166-3542(95)00970-1

After interferon (IFN) treatment of patients with condyloma acuminatum, groups clinically proven to be responders or nonresponders were selected, and cellular parameters that might influence the clinical response were studied in pretreatment biopsies by reverse transcription polymerase chain reaction (RT-PCR). The nonresponders were found to express higher amounts of cellular proliferative markers, such as proliferating cell nuclear antigen (PCNA), cyclin A, and cdc2 kinase, but lower levels of growth suppressor genes (TGF-β1, TGF-β2 and p53) before IFN treatment. The responders retained the epidermal keratinization, except for some signs of hyperproliferation (K6, K16 cytokeratins). In addition, the nonresponders showed a shift in the keratinization pattern to a mucosal or fetal type, as evidenced by high expression of the K18, K6, K16 and K13 cytokeratins but decreased K5, K14 and K10 levels before treatment. The expression of the human papillomavirus (HPV) genes is consistent with these differentiation patterns. The crucial conclusion to be drawn from this study is that those condylomas whose pretreatment phenotype most closely resembles that of normal epidermis respond to IFN treatment, whereas those more akin to nonkeratinizing epithelia fail to respond, i.e. the resistance of condylomas to IFN treatment is correlated with dedifferentiation.