EXPRESSION OF PCNA IS ASSOCIATED WITH THE PRESENCE OF HPV DNA IN SKINWARTS

A series of 90 excised cutaneous warts (verrucae vulgaris) were studie d for the presence of HPV (human papillomavirus) DNA using in situ hyb ridization (ISH) with biotinylated full genomic DNA probes of HPV type s 1, 2, 3 and 4, The expression of PCNA (proliferating cell nuclear an tigen) was examined using conventional immunohistochemistry. The aim w as to test the hypothesis that HPV can reactivate PCNA, including in t he host replication machinery, HPV DNA of the above types was detected in 60 of 90 verruca biopsies studied (66.7%): HPV 2 in 56 cases, HPV 1 in 2 cases, and HPV 3 in 2 cases. PCNA was expressed in all samples except two, The signal distribution of HPV DNA markedly differed from that of PCNA expression, ISH revealed strong HPV DNA signals in both t he granular and the upper spinous cell layers, the most intense signal s being detected in the upper epidermis, On the other hand, nuclear PC NA staining was present in the majority of parabasal and basal cells, Although strong PCNA signals within the wart lesions were found in the areas where HPV DNA was present, the PCNA positivity was almost invar iably localized in the differentiated cells of the spinous cell layers , just below the HPV DNA-expressing cells, At the margins of the lesio ns, PCNA expression was still strong but disappeared abruptly towards the normal epidermis, HPV DNA-positive warts showed more intense expre ssion of PCNA than did the HPV DNA-negative ones in this study, Our re sults indicate that PCNA induction is associated with the presence of HPV DNA, suggesting that HPV can reactivate PCNA, thus interfering wit h the host cell DNA replication machinery.