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The purpose of this study was to determine the extent of p63 immunoreactivity in the malignant salivary gland neoplasms adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare this to the expression of this marker in the benign salivary gland tumors canalicular adenoma and basal cell adenoma. Few studies on the expression of p63 in head and neck salivary gland tumors have been published to date. P63, a selective immunohistochemical marker of basal/stem cells of stratified epithelium and of myoepithelial cells, is a p53 homologue that plays an essential role in both morphogenesis of epidermis and limb development. P63 immunoreactivity has been demonstrated in squamous cell and urothelial carcinomas. It is generally absent in most nonsquamous cell carcinomas.Formalin-fixed paraffin-embedded sections from 49 salivary gland neoplasms, representing 6 canalicular adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to 2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY, were stained with an anti-p63 monoclonal antibody.Nuclear p63 reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was also identified in the majority of cases of ACC (13/15, 87%), primarily in the nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of parotid origin stained strongly for p63, with staining localized to the peripheral tumor cells situated adjacent to the connective tissue stroma. None of the basal cell adenomas originating in the upper lip stained with p63. In native adjacent salivary gland tissue, p63 reactivity was identified focally in the nuclei of myoepithelial and basal duct cells.P63 is strongly expressed in basal cell adenoma of parotid origin, and in ACC and PLGA. Canalicular adenoma did not demonstrate p63 staining, consistent with this tumor's putative luminal ductal cell differentiation. Our results suggest that the neoplastic cells in PLGA may represent either a population of p63-positive epithelial stem/reserve cells similar to the basal cells of stratified epithelium, or modified myoepithelial cells. Given the staining pattern of the tumors examined, p63 does not appear to be an ideal marker for distinguishing between ACC, PLGA, and basal cell adenoma.