Molecular Pathologic Analysis for Mechanisms of Multistep Carcinogenesis of Malignant Transformation in Salivary Gland Pleomorphic Adenoma

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To clarify the mechanisms of multistep carcinogenesis of malignant transformation in salivary gland pleomorphic adenoma, pathologic analysis has been done using histologic specimens taken from carcinoma ex pleomorphic adenoma cases. Histologically, malignant component was high-grade carcinoma and in the early stage of development, carcinoma cells proliferated replacing by ductal structures of pre-existing pleomorphic adenoma. Immunohistochemical study revealed that carcinoma component had high proliferative activities and was frequently positive for p53 and HER2/neu. Molecular analysis demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the carcinoma component, but no genetic alterations have been detected in the H-, K-, and N-ras genes. More elaborated studies would be necessary to further progress in this field.