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

Takuya Yoshimura,Hirotaka Takayama,Akihide Tanimoto,Norifumi Nakamura,Mitsuharu Nomoto,Shotaro Higashi,Yuka Hirano,Takayuki Ishida,Sohsuke Yamada,Masaru Yamashita,Hajime Suzuki,Hirotsugu Noguchi

doi:10.3390/cancers14010054

Abstract

Simple SummaryMucoepidermoid carcinoma (MEC) is the most common malignancy of all salivary neoplasms, and no effective treatment strategy for MEC has been established other than resection. In this study, we showed that Purkinje cell protein (PCP) 4/peptide (PEP) 19 and human epidermal growth factor receptor 2 (HER2) are predicted to play important roles in the pathogenesis and progression of MEC. The detection of PCP4/PEP19 and HER2 may be useful for providing more effective treatments against MEC.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.

Highlights

Salivary gland carcinomas are a rare and clinically diverse group of neoplasms, among which mucoepidermoid carcinoma (MEC) is the most common malignancy, representing10 to 15% of all salivary neoplasms [1]
We previously reported the usefulness of MUC4 and MUC6 in predicting the prognosis of MEC [6], so a classification system according to the molecular expression status may be useful for selecting appropriate therapies, such as molecular-targeted chemotherapy
The results showed that Purkinje cell protein 4 (PCP4)/PEP19 positivity and Human epidermal growth factor receptor 2 (HER2) negativity were significantly correlated with prognosis (Figure 2A,C, p < 0.05), while no significant correlation was observed between prognosis and epidermal growth factor receptor (EGFR) expression (Figure 2B)

Summary

Introduction

Salivary gland carcinomas are a rare and clinically diverse group of neoplasms, among which mucoepidermoid carcinoma (MEC) is the most common malignancy, representing10 to 15% of all salivary neoplasms [1]. Gefitinib has been reported to be effective in lung MEC [3], and no effective treatment strategy for MECs of salivary glands has been established other than resection. Cases of successful molecular-targeted therapy have been reported but have not been established. We previously reported the usefulness of MUC4 and MUC6 in predicting the prognosis of MEC [6], so a classification system according to the molecular expression status may be useful for selecting appropriate therapies, such as molecular-targeted chemotherapy. The majority of salivary gland carcinomas, including MECs, are characterized by recurrent gene fusions, which proved to be highly valuable diagnostically, but less in terms of therapy; for that reason, there is a strong need to find new markers that could be used in molecular-targeted therapies [7,8]

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