title: Epidermal growth factor receptor expression and KRAS and BRAF mutations: study of 39 sinonasal intestinal-type adenocarcinomas.
abstract: Sinonasal intestinal-type adenocarcinomas (ITACs) are uncommon tumors of poor prognosis defined by their similarities to colorectal adenocarcinomas. The involvement of the epidermal growth factor receptor (EGFR) pathway in colorectal adenocarcinoma oncogenesis is well established, and the same is expected to apply to ITACs. In a series of 39 ITACs, we investigated EGFR amplification and chromosome 7 polysomy by fluorescence in situ hybridization; EGFR, KRAS, and BRAF mutational status by polymerase chain reaction sequencing; EGFR variant messenger RNA expression by quantitative reverse transcriptase polymerase chain reaction; and EGFR protein expression by immunohistochemistry with antibodies targeting the extracellular domain, the intracellular domain, and the phosphorylated isoform. The findings were analyzed with respect to clinical data, histologic typing, and patient outcome. EGFR amplification was observed in 3 cases with a focal distribution. EGFR proteins were overexpressed in all these foci with both extracellular domain and intracellular domain antibodies, suggesting involvement of the whole receptor. Chromosome 7 polysomy was observed in 15 cases and was not associated with EGFR protein expression. EGFR, KRAS, or BRAF mutations were observed in 5 different cases. The EGFRvIII mutant was not detected. In all cases, EGFR variants were expressed. There was no association between these molecular features and patient survival. In conclusion, (1) our study revealed various EGFR expression patterns in ITACs, indicating tumor heterogeneity; (2) EGFR amplification should be distinguished from chromosome 7 polysomy; (3) fluorescence in situ hybridization analysis could be guided by immunohistochemistry; and (4) ITACs share common alterations of the EGFR pathway with colorectal adenocarcinomas, except for a lower frequency of KRAS and BRAF mutations.
authors.affiliation: Department of Pathology, Dupuytren University Hospital, 2 Avenue Martin Luther King, 87042 Limoges, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Projetti
authors.forename: Karine
authors.initials: K
authors.lastname: Durand
authors.forename: Alain
authors.initials: A
authors.lastname: Chaunavel
authors.forename: Sophie
authors.initials: S
authors.lastname: Léobon
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lacorre
authors.forename: François
authors.initials: F
authors.lastname: Caire
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bessède
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Moreau
authors.forename: Béma
authors.initials: B
authors.lastname: Coulibaly
authors.forename: François
authors.initials: F
authors.lastname: Labrousse
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D010255:Paranasal Sinus Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: EGFR; EGFR amplification; EGFR copy number gain; EGFR immunohistochemistry; Sinonasal intestinal-type adenocarcinoma