Epidermal growth factor receptor expression and KRAS and BRAF mutations: study of 39 sinonasal intestinal-type adenocarcinomas

Study of MET protein levels andMETgene copy number in 72 sinonasal intestinal-type adenocarcinomas

“…We determined MET gene copy number gain because of gene amplification and/or chromosome 7 polysomy. Each tissue core was scored as follows: (1) MET gene amplification according to one of the following criteria: a MET to CEN7 ratio of at least 2 for all nuclei, or gene clusters scored in at least 10% of nuclei, or at least 15 copies of MET in at least 10% of nuclei; (2) chromosome 7 polysomy, with at least 3 CEN7 copies observed in more than 30% of nuclei; and (3) normal copy number for MET : samples with no gene amplification or polysomy. For each tumor, the highest MET gene copy number was selected for statistical analyses.…”

“…Several studies have reported interactions and synergy between the MET and epidermal growth factor receptor (EGFR) pathways . In addition, recent reports have indicated that, as in CRA, EGFR protein expression is a common feature of ITACs …”

Genomic profiling of intestinal‐type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes

“…Nuclear β‐catenin expression was observed in approximately 30%–50% . KRAS mutations were detected in 15% of ITAC, but none in B‐type Raf (BRAF), epidermal growth factor receptor (EGFR), and adenomatous polyposis coli (APC) . Immunohistochemical studies on different receptor tyrosine kinases have shown 20%–30% EGFR, 8% erb‐b2 receptor tyrosine kinase 2 (ERBB2), 64% cMET proto‐oncogene, receptor tyrosine kinase (MET), and 0% anaplastic lymphoma receptor tyrosine kinase (ALK) overexpression, whereas fibroblast growth factor receptor 1 (FGFR1) gene copy number amplifications were absent .…”

“…KRAS mutations were detected in 15% of ITAC, but none in B‐type Raf (BRAF), epidermal growth factor receptor (EGFR), and adenomatous polyposis coli (APC) . Immunohistochemical studies on different receptor tyrosine kinases have shown 20%–30% EGFR, 8% erb‐b2 receptor tyrosine kinase 2 (ERBB2), 64% cMET proto‐oncogene, receptor tyrosine kinase (MET), and 0% anaplastic lymphoma receptor tyrosine kinase (ALK) overexpression, whereas fibroblast growth factor receptor 1 (FGFR1) gene copy number amplifications were absent . The etiological factors wood and leather dust are not considered mutagenic, which is the reason why a role for inflammatory processes caused by a prolonged irritation by wood and leather particles has been suggested in ITAC tumorigenesis .…”

“…13,17,[19][20][21][22][23][24] Immunohistochemical studies on different receptor tyrosine kinases have shown 20%-30% EGFR, 8% erb-b2 receptor tyrosine kinase 2 (ERBB2), 64% cMET proto-oncogene, receptor tyrosine kinase (MET), and 0% anaplastic lymphoma receptor tyrosine kinase (ALK) overexpression, whereas fibroblast growth factor receptor 1 (FGFR1) gene copy number amplifications were absent. 22,23,[25][26][27][28] The etiological factors wood and leather dust are not considered mutagenic, which is the reason why a role for inflammatory processes caused by a prolonged irritation by wood and leather particles has been suggested in ITAC tumorigenesis. 15,29,30 In accord with this hypothesis, cyclooxygenase-2 (COX-2) expression has been observed in up to 50% of ITAC and was correlated with wood dust but not tobacco exposure.…”