title: Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas.
abstract: OBJECTIVE
  Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors.
  
  
  METHODS
  This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS.
  
  
  RESULTS
  In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient's age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13.
  
  
  CONCLUSIONS
  Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs.
  
  
  CONCLUSIONS
  The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.
authors.affiliation: Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schneider
authors.affiliation: Institute for Pathology, University Hospital Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Strehl
authors.affiliation: Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Linz
authors.affiliation: Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Brands
authors.affiliation: Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Beckford
authors.affiliation: Institute for Pathology, University Hospital Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors.forename: A C
authors.initials: AC
authors.lastname: Kübler
authors.affiliation: Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany. mueller_u2@ukw.de.
authors.forename: U D A
authors.identifier: http://orcid.org/0000-0001-7869-7686
authors.initials: UD
authors.lastname: Müller-Richter
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D003062:Codon; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010766:Phosphorylation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; C117307:KRAS protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Adenoid cystic carcinoma; Cetuximab; EGFR; KRAS; Salivary gland cancer