Is the epidermal growth factor receptor status in lung cancers reflected in clinicopathologic features?
BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are molecular-targeted drugs that are innovatively effective for non-small cell lung carcinomas with EGFR mutations. Epidermal growth factor receptor is a transmembrane receptor forming dimers on ligand binding. These then stimulate signals by activating receptor autophosphorylation through tyrosine kinase activity. Autophosphorylation triggers intracellular pathways facilitating malignant conversion. The most clinically advanced EGFR inhibition strategies include small-molecule inhibition of the intracellular tyrosine kinase domain (gefitinib and erlotinib) and monoclonal antibody-mediated blockade of the extracellular ligand-binding domain (cetuximab). Lung cancers with EGFR mutations are prevalent among patients who are female, of Asian ethnicity, and nonsmokers; thus, they can obtain benefit from EGFR tyrosine kinase inhibitors.


OBJECTIVE
To survey histopathologic findings and examine correlations with EGFR mutations. We mainly focused on component cell types (hobnail, columnar, and polygonal) and presence or absence of bronchioloalveolar carcinoma elements and a micropapillary pattern. Although EGFR mutations can be detected by various methods, including polymerase chain reaction-Invader assay or direct sequencing, these are inconvenient.


METHODS
Review of the published literature.


CONCLUSIONS
Detailed pathologic examination showed significant genotype-phenotype correlations between EGFR mutations and presence of a bronchioloalveolar carcinoma component, a micropapillary pattern, and the hobnail cell type. We conclude that these characteristic histologic features are good predictors of EGFR mutations, and patients with these features might be good candidates for and could benefit from therapy with EGFR tyrosine kinase inhibitors.
Inamura
Kentaro
K
Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
Ninomiya
Hironori
H
Ishikawa
Yuichi
Y
Matsubara
Osamu
O
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases