Proliferation and invasion factors in HIV-associated dysplastic and nondysplastic oral warts and in oral squamous cell carcinoma: an immunohistochemical and RT-PCR evaluation.

Abstract

Oral warts arising in human immunodeficiency virus (HIV) infection occasionally show marked epithelial dysplasia. However, anecdotal evidence suggests that they do not progress to oral squamous cell carcinoma (SCC). Therefore, we evaluated lesions for expression of proteins (tenascin-C, beta6 integrin, and matrix metalloproteinase-1[MMP1]) that have been identified as important in the invasive phase of oral SCC. Twenty-two oral dysplastic warts from 22 patients and 5 oral SCCs were stained for human papillomavirus (HPV) antigen, proliferation protein Ki-67, tenascin-C, beta6, and MMP1 by immunohistochemical methods. For comparison, 5 nondysplastic warts each from HIV-positive and HIV-negative patients and 5 normal mucosa specimens were included. Sections were semiquantitatively assessed, and results were compared. Because MMP1 was the lowest or least expressed interface protein, MMP1 mRNA was quantitatively assessed from formalin-fixed paraffin-embedded tissue in selected cases with quantitative reverse transcription-polymerase chain reaction. Twenty of 22 dysplastic warts stained positive for human papillomavirus common antigen, and all warts showed high proliferative fractions similar to SCCs. Tenascin-C and beta6 were variably expressed by the dysplastic warts but were consistently expressed at high levels in the SCCs. MMP1 protein levels were negative or low in 20 of 22 in dysplastic warts, but were elevated in 4 of 5 SCCs. MMP1 mRNA analysis indicated that message was low in 4 dysplastic warts and also suggested that protein translation was incomplete in 3 of the warts. We conclude that invasion-associated proteins are underexpressed in oral dysplastic warts in HIV-positive men. However, until these patients are followed for extended periods, the risk of development of SCC from oral dysplastic warts remains unknown.