Dysregulation of the Rb pathway in recurrent pleomorphic adenoma of the salivary glands

Abstract

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and while mostly benign, recurrences (RPA) and malignant transformation to carcinoma ex-PA (CXPA) do occur. Cell cycle proteins important in its tumorigenesis have been studied as markers for PA with a high risk of RPA or CXPA. The aim of the present study was to investigate cell cycle markers p-16, cyclin D1, CDK4, E2F, and retinoblastoma (Rb) in this context. Expression of p16, cyclin D1, E2F, CDK4, and Rb was studied by immunohistochemistry in 24 cases of PA, 21 of RPA, and 2 of CXPA. The presence of HPV was assessed by in situ hybridization. Immunostaining for p16 and cyclin D1 was negative or weakly positive in most cases of PA while strongly positive in the majority of RPA and both CXPA cases. Staining for Rb and CDK4 was either negative or weakly positive in PA, RPA, and CXPA. Expression of E2F was stronger in RPA and CXPA than in PA. Nuclear reactivity for HPV was not observed in any case. In conclusion, the strong staining for p16, cyclinD1, and E2F in RPA and CXPA, while weak or negative in PA, suggests that these proteins might be involved in recurrence and malignant transformation of PA.

PLAG1 expression is maintained in recurrent pleomorphic adenoma

“…Recurrent tumors actively proliferate, and one would expect in recurrent tumor upregulation of the expression of cell proliferation regulatory proteins. This was effectively reported by De Souza et al [14], who described strong staining for p16, cyclin D1, and E2F in RPA. In PA, the expression of these markers appeared to be weakly positive or negative, suggesting that these proteins might be involved in PA recurrence.…”

Recurrent Benign Salivary Gland Neoplasms

“…Brieger et al [5] have found that cadherin 11, an adhesion protein, and fascin, a bundling protein with possible roles in cell motility and detachment of tumor cells, are both over-expressed in tumors that subsequently recur. More recently, de Souza et al [6] performed immunohistochemical analyses to investigate the expression of cell cycle proteins in PA, RPA, and carcinoma ex-pleomorphic adenoma (CXPA). In contrast with PA, RPA and CXPA demonstrated strong staining for p16, cyclin D1, CDK4, E2F, and retinoblastoma protein.…”

Expression of p16Ink4aprotein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course

“…On the other hand, Tarakji et al 15 16 revealed a significant difference in p16 Ink4a expression between NSGT and CaexPA; they, however, demonstrated higher expression in NSGT and lower in CaexPA. de Souza et al performed p16 Ink4a nuclear expression analysis and revealed strong staining in recurrent PA and CaexPA, while PA was weakly staining or negative, suggesting that p16 Ink4a may be involved in the recurrence and malignant transformation of PA. 39 Others confirm p16 Ink4a overexpression in various salivary Table 4 The percentage distribution of p16 Ink4a immunohistochemical staining in the CaexPA group in reference to survival rate…”