title: Concomitant expression of ezrin and HER2 predicts distant metastasis and poor prognosis of patients with salivary gland carcinomas.
abstract: Salivary gland carcinomas (SGCs) exhibit heterogeneous biological behaviors, including the formation of distant metastases, which is a critical event associated with poor prognosis. Ezrin, which is a member of the ezrin-radixin-moesin family of plasma membrane-cytoskeleton linker proteins, may provide a marker for metastasis and poor survival of patients with cancer. The aim of the present study was to investigate the relationship between ezrin expression and the expression of HER2, p53, and Ki-67 as well as clinicopathological factors in SGCs. For this purpose, we used immunohistochemistry to analyze the expression of these proteins in tissue microarrays prepared from formalin-fixed, paraffin-embedded primary tumor tissues of 221 patients with SGCs. Using receiver operating characteristic curves, we determined cut-off values of 30% and 5.0% for high expression of ezrin and Ki-67, respectively. High ezrin expression detected in samples from 63 (28.5%) patients with SGCs significantly correlated with male sex, high-grade histopathology, high Ki-67 labeling index, HER2 overexpression, aberrant expression of p53, and distant metastasis. Multivariate analysis demonstrated that high ezrin expression was an independent prognostic factor for shorter overall survival (hazard ratio, 2.11 [1.09-4.05]; P=.027). Furthermore, concomitant high expression of ezrin and HER2 overexpression correlated significantly with shorter disease-free survival and overall survival as well as a high incidence of distant metastasis (P<.001). These findings indicate that ezrin and HER2 expression in patients with SGCs represents a high-grade histopathological subtype that requires adjuvant therapy, including molecularly targeted therapies, to decrease the risk of subsequent metastasis.
authors.affiliation: Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan; Department of Otolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: hkazuki@med.kyushu-u.ac.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan. Electronic address: rhayashi@east.ncc.go.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan. Electronic address: tmukaiga@east.ncc.go.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mukaigawa
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan. Electronic address: manyamaz@dent.niigata-u.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan. Electronic address: sfujii@east.ncc.go.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D016009:Chi-Square Distribution; D003598:Cytoskeletal Proteins / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012307:Risk Factors; D012468:Salivary Gland Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D013997:Time Factors; D046888:Tissue Array Analysis; D015854:Up-Regulation; D055815:Young Adult; D000099149:Ezrin
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000099149:Ezrin; C508053:ERBB2 protein, human
keywords: Distant metastasis; Ezrin; HER2; Molecularly targeted therapy; Salivary gland carcinoma