Proliferative verrucous leukoplakia (PVL) is a highly persistent and aggressive oral pre-malignant lesion with an obscure etiopathogenesis and a malignant transformation rate of 85-100%. AIMS: The aim of the present study is to assess the role of Ki-67, p16, CD34, Bcl-2, cyclooxygenase-2 (COX-2) in the spectrum of PVL to ascertain their role in its etiopathogenesis. SETTINGS AND DESIGN: A retrospective chart analysis was carried out on a series of seven confirmed cases of PVL, which were followed-up for 2 years. SUBJECTS AND METHODS: Immunohistochemical appraisal of these cases was carried out by a panel of markers, related to cell proliferation, cell cycle regulation, angiogenesis, apoptosis and inflammation. The expression of these markers was correlated with patients' clinicopathological profile. STATISTICAL ANALYSIS USED: The frequency distribution of the group data was analyzed. RESULTS: The latest labeling index of Ki-67 in our cases ranged from 8.18 to 12.6. p16 was positive in 3/7 cases. Bcl-2 expression was moderately positive in 2/7 cases. All cases were intensely positive for COX-2 staining. Microvascular density assessed by CD34 staining ranged from 11 to 20/high power fields. One case which transformed into squamous cell carcinoma demonstrated increased Ki-67, Bcl-2, COX-2, CD34 expression, but negative p16 and Bcl-2 expression. CONCLUSIONS: Application of these markers in understanding the behavior of PVL suggests that an imbalance between the proliferation apoptosis dynamics of the lesion accompanied by an increase in inflammation and angiogenesis underlie the molecular pathogenesis of the PVL spectrum.
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