PCP4/PEP19 and HER2 Are Novel Prognostic Markers in Mucoepidermoid Carcinoma of the Salivary Gland

Abstract

Mucoepidermoid carcinoma (MEC) is one of the most common malignant salivary gland carcinomas, but no effective treatment strategy has been established other than surgical resection. Purkinje cell protein (PCP) 4/peptide (PEP) 19 is a calmodulin-binding antiapoptotic peptide that is expressed and inhibits apoptosis in human breast cancer cells. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor that has been implicated in the pathogenesis of many carcinomas, particularly breast and gastric carcinomas. In the present study, we performed immunohistochemical analyses of samples from 73 patients who underwent surgical resection for MEC of the salivary gland using antibodies against PCP4/PEP19 and HER2. PCP4/PEP19 expression was related to better prognosis, while HER2 expression was associated with worse prognosis. Patients that were PCP4/PEP19-positive and HER2-negative showed similar outcomes to PCP4/PEP19 and HER2 alone. Therefore, PCP4/PEP19 and HER2 are predicted to play important roles in the pathogenesis and progression of MEC.

Keywords: Purkinje cell protein 4/peptide 19; human epidermal growth factor 2; mucoepidermoid carcinoma; prognosis; salivary gland.

Figure 1

Representative immunohistochemical staining of PCP4/PEP19. (A) EGFR and HER2; (B) expression in MECs. PCP4/PEP19 expression was judged to be positive if cytoplasmic and nucleic staining was observed in 1% or more of tumor cells. The criteria of positive expression for HER2 were determined by reference to previous reports; that is, the score was divided into four categories (0, 1+, 2+, 3+) according to the membrane staining of tumor cells, and a score of 2+ or more was judged to be positive. Purkinje cell protein 4 (PCP4)/peptide (PEP) 19, brain-specific polypeptide; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor type 2; MEC, mucoepidermoid carcinoma.

Figure 2

Kaplan–Meier curves for the DFS and DSS of MEC patients within the first five years after surgery, according to PCP4/PEP19 (A); EGFR (B); and HER2 (C) expression. Since PCP4/PEP19 and HER2 were significantly related to DSS and DFS, the Kaplan–Meier curve is shown for combined expression (D). DFS, disease-free survival; DSS, disease-specific survival; MEC, mucoepidermoid carcinoma; Purkinje cell protein 4 (PCP4)/peptide (PEP) 19, brain-specific polypeptide; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor type 2; PEP19(+)HER2(+), PCP4/PEP19-positive and HER2-positive; PEP19(+)HER2(−), PCP4/PEP19-positive and HER2-negative; PEP19(−)HER2(+), PCP4/PEP19-negative and HER2-positive; PEP19(−)HER2(−), PCP4/PEP19-negative and HER2-negative.

Figure 2

Kaplan–Meier curves for the DFS and DSS of MEC patients within the first five years after surgery, according to PCP4/PEP19 (A); EGFR (B); and HER2 (C) expression. Since PCP4/PEP19 and HER2 were significantly related to DSS and DFS, the Kaplan–Meier curve is shown for combined expression (D). DFS, disease-free survival; DSS, disease-specific survival; MEC, mucoepidermoid carcinoma; Purkinje cell protein 4 (PCP4)/peptide (PEP) 19, brain-specific polypeptide; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor type 2; PEP19(+)HER2(+), PCP4/PEP19-positive and HER2-positive; PEP19(+)HER2(−), PCP4/PEP19-positive and HER2-negative; PEP19(−)HER2(+), PCP4/PEP19-negative and HER2-positive; PEP19(−)HER2(−), PCP4/PEP19-negative and HER2-negative.