EGFR autophosphorylation but not protein score correlates with histologic and molecular subtypes in lung adenocarcinoma

Judit Moldvay, Tamás Barbai, Krisztina Bogos, Violetta Piurko, János Fillinger, Helmut H. Popper, József Tímár

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Established clinicopathologic characteristics of non- small cell lung cancer patients define a subgroup responding better to EGFR-TK inhibitors: adenocarcinoma histology, ethnicity, sex, smoking status, presence of activating EGFR mutation, and/or K-RAS wild type. However, EGFR mutation does not automatically lead to increased activity of the protein influenced by several factors. As adenocarcinoma can be further divided into histologic subclasses, we compared adenocarcinomas without lepidic growth pattern (NLAC) to those characterized by pure or predominant lepidic growth (LAC) for EGFR protein expression and autophosphorylation activity (Y1173), as determined by immunohistochemistry. This pretarget therapy cohort comprised a total of 110 surgically operated patients of stage I non-small cell lung cancer: 49 NLAC and 61 LAC variants. The LAC group had a significantly better prognosis and the incidence of phospho-EGFR-positive tumors was significantly higher compared with NLAC. Patient sex did not influence EGFR activity, but the incidence of pEGFRpositive tumors was significantly lower among smoker patients. There was no statistically significant difference in EGFR or KRAS mutation frequencies between the 2 groups. In NLAC, pEGFR-positive tumors occurred exclusively among EGFRmutant/ K-RAS wild-type tumors. On the contrary, in LAC tumors, pEGFR-positive tumors were similarly frequent in the EGFR or K-RAS mutant groups indicating an interesting feedback activation of EGFR signaling in K-RAS mutant tumors. Our data also indicate that EGFR mutation leads to EGFR autophosphorylation only in a small fraction of adenocarcinoma patients, which might have clinical significance.

Original languageEnglish
Pages (from-to)204-209
Number of pages6
JournalDiagnostic Molecular Pathology
Volume22
Issue number4
DOIs
Publication statusPublished - Dec 1 2013

Keywords

  • Autophosphorylation
  • EGFR
  • Immunohistochemistry
  • K-RAS
  • Lung adenocarcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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