title: Expression of amphiregulin in mucoepidermoid carcinoma of the major salivary glands: a molecular and clinicopathological study.
abstract: In mucoepidermoid carcinoma (MEC), CRTC1-MAML2 fusion indicates a favorable prognosis. Amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, has been shown to be a downstream target of CRTC1-MAML2 fusion, and to play a role in tumor growth and survival in CRTC1-MAML2-positive MEC cell lines. The aim of this study was to characterize the AREG and EGFR expression in the fusion-positive and fusion-negative MEC of the major salivary gland. The AREG and EGFR expression were studied by immunochemistry in 33 MEC cases of the major salivary glands. CRTC1-MAML2 fusion was tested by reverse-transcription polymerase chain reaction (23 CRTC1-MAML2 fusion-positive, 10 fusion-negative). Of 23 fusion-positive cases, AREG and EGFR overexpression were detected in 17 (73.9%) and 14 (60.9%) cases, respectively. Of 10 fusion-negative cases, AREG and EGFR overexpression were detected in 1 (10%) and 3 (30.0%) cases, respectively. There was a positive correlation between CRTC1-MAML2 fusion and AREG overexpression (P < .01), but not between CRTC1-MAML2 fusion and EGFR overexpression. The AREG overexpression was associated with a longer disease-free survival of the MEC patients (P = .042), but EGFR overexpression was not. In this study, we showed that AREG overexpression was detected more frequently in the CRTC1-MAML2 fusion-positive tumors than in fusion-negative tumors. Detection of AREG expression may be useful for identifying CRTC1-MAML2-positive MECs and as a marker for favorable prognosis.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan. Electronic address: takami@med.kobe-u.ac.jp.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shinomiya
authors.affiliation: Department of Pathology and Molecular Diagnostics, Nagoya City University Postgraduate School of Medical Sciences, Nagoya, 467-8601, Japan; Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, 464-8651, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Otorhinolaryngology, Hyogo Cancer Center, Akashi, 673-8558, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yonezawa
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Otsuki
authors.affiliation: Department of Otorhinolaryngology, Hyogo Cancer Center, Akashi, 673-8558, Japan.
authors.forename: Shigemichi
authors.initials: S
authors.lastname: Iwae
authors.affiliation: Department of Pathology and Molecular Diagnostics, Nagoya City University Postgraduate School of Medical Sciences, Nagoya, 467-8601, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Nibu
mesh_terms: D000368:Aged; D066258:Amphiregulin / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D050939:Gene Fusion; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D014408:Biomarkers, Tumor; C500984:CRTC1 protein, human; D004268:DNA-Binding Proteins; C471297:MAML2 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: AREG; CRTC1-MAML2; EGFR; Mucoepidermoid carcinoma; Prognosis