Expression profiles of p53, p63, and p73 in benign salivary gland tumors

Abstract

The tumor-suppressor protein p53 has recently been shown to belong to a family that includes two structurally related proteins, p63 and p73. In contrast to p53, p63 and p73 play an essential role in epithelial development, stem cell identity and cellular differentiation. Salivary gland tumors carry a wide spectrum of histopathological forms, which may share a common single-cell origin from the epithelial progenitor basal duct cells and have a different tendency of malignant progression. This study was performed to examine the expression of p53, p63, and p73 in benign salivary gland tumors. Expression and mutation of p53, p73, and p63 were examined by direct DNA sequencing, reverse transcription PCR using isoform-specific primers, and by immunohistochemistry in normal parotid tissue ( n=10), and various tumors of the salivary gland (42 pleomorphic adenomas, 12 myoepitheliomas, 8 basal cell adenomas, 5 oncocytomas, 5 canalicular adenomas, and 20 adenolymphomas). In normal parotid tissue the expression of p63 and p73 was restricted to few basal and myoepithelial cells. Ductal luminal and acinus cells were completely negative for the expression of all three family members. In contrast, in salivary gland tumors, strong nuclear staining for p63 and p73 was observed. Myoepithelial and basaloid cells and the basal epithelial layer of adenolyphomas and oncocytomas were positive for p63 and also, to a lesser extent, to p73. Mutations of p53 were detected in 4 of 42 (10%) pleomorphic adenomas, in 3 of 12 (25%) myoepitheliomas, and in 1 of 8 (13%) basal cell adenomas but not in other tumors. We failed to detect specific mutations of p63 and p73. Using isoform-specific PCR, we found that all isoforms of p63 were expressed in normal parotid tissue whereas the pleomorphic adenomas, myoepitehliomas, and basal cell adenomas dominantly expressed the transactivation-incompetent truncated isoforms. Our data indicate that p63 and p73 are upregulated in salivary gland tumors and may serve as a marker of epithelial and myoepithelial progenitor cells in salivary glands. The prevalence of p53 mutations and the observation of the expression of DeltaNp63 isoforms only in pleomorphic adenomas, myoepitheliomas, and also basal cell adenomas may reflect their possible malignant potential.

Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules

“…Salivary pleomorphic adenomas frequently showed the coexpression of CKs and vimentin, and moreover, neoplastic myoepithelial cells in these tumors revealed positivity for p63. 16,17 Such findings supported that matrix-producing carcinoma of the breast was associated with myoepithelial cell-like differentiation: although the metaplastic cells of matrixproducing carcinoma have myoepithelial cell-like features, the origin of this cancer is considered to be derived from mammary epithelial cells. A recent report showed that CD99 (MIC2) was expressed in breast carcinoma, especially in matrix-producing carcinoma, but concluded that there was no significance between CD99 (MIC2) expression and the proliferating rate or nodal status; 18 however, it was suggested that CD99 (MIC2) expression was a useful marker to differentiate metaplastic carcinomas from primary or metastatic sarcomas of the breast, although its biological significance remains unclear.…”

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma

“…Benign myoepithelial cells of salivary gland, like those of normal breast and prostate epithelium, express p63. 21 Di Como et al 9 reported p63 expression in four pleomorphic adenomas and two of four carcinomas of the salivary glands. Bilal et al found that for all salivary gland-derived tumor types that differentiated towards luminal and myoepithelial lineages (pleomorphic adenomas, basal cell adenomas, and adenoid cystic carcinomas), p63 was expressed in myoepithelial cells, whereas internal luminal cells were always negative.…”

Assessment of TP53 mutations in benign and malignant salivary gland neoplasms

“…SSCP can miss mutations detected by direct sequencing. Weber and co-workers analyzed TP53 mutations by direct sequencing of exons 4-9 and detected mutations in 4/42 PA and 3/12 myoepitheliomas [14]. Despite the evidence that TP53 might be altered in SGN [10,13,14,16,17,18], we sequenced all of our samples and found only four missense mutations, one nonsense TP53 mutation and a very low frequency of LOH at the 17p 13.1 region in our subset of salivary tumor samples.…”

“…Previous papers reported positive immunoexpression of p53 protein [8,9], yet TP53 mutations seem to be infrequent events in pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), mucoepidermoid carcinomas (MEC) and carcinomas ex pleomorphic adenomas (CAexPA) [10,11,12,13,14]. These previous papers relied on different techniques (SSCP, for example, which misses mutations when compared to direct sequencing), and in some of them, sequencing was only performed on a few samples.…”