Immunohistochemical Features of an Atypical Pleomorphic Adenoma of the Salivary Gland-Overexpression of Ki-67 and p53

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Atypical pleomorphic adenoma (APA) is a premalignant condition of pleomorphic adenoma (PA), and APA with hypercellularity (h-APA) is seldom positive for HER2/neu. Whether h-APA cells show higher mitotic activity and oncogenic mutations remains unclear. Thirteen cases of h-APA, 10 cases of carcinoma (Ca) -ex-PA, and 19 cases of PA were immunohistochemically examined for overexpression of the proliferation marker protein, Ki-67 and the tumor suppressor protein, p53. Ki-67 expression is higher in Ca-ex-PA than in other groups, and it is also higher in h-APA than in PA. p53 expression is also higher in Ca-ex-PA than in other groups, but there is no difference between h-APA and PA. We hypothesize the sequence of events during carcinogenesis of PA as follows: first there is an increase in proliferation in PA, which leads to h-APA, secondly, there is an amplification of the HER2/neu oncogene in h-APA and finally, p53 overexpression occurs in h-APA and leads to Ca-ex-PA. This hypothesis explains the increase in both patients' age and tumor size in each group, in the sequence from PA to Ca-ex-PA via h-APA.