Epidermal growth factor receptor (EGFR) high gene copy number and activating mutations in lung adenocarcinomas are not consistently accompanied by positivity for EGFR protein by standard immunohistochemistry

Ferenc Pinter, Judit Papay, Andrea Almasi, Zoltan Sapi, Edit Szabo, Melinda Kanya, Anna Tamasi, Balazs Jori, Edit Varkondi, Judit Moldvay, Klara Szondy, Gyorgy Keri, Massimo Dominici, Pierfranco Conte, Sandor Eckhardt, Laszlo Kopper, Richard Schwab, Istvan Petak

Research output: Contribution to journalArticlepeer-review

Abstract

The purpose of this study was to investigate whether detectable protein biomarker overexpression is a prerequisite for the presence of increased gene copy number or activating mutations and responsiveness to the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib in patients with lung adenocarcinomas. EGFR status was prospectively analyzed in tumor biopsy samples by three methods: protein expression (n = 117) by standardized immunohistochemistry (IHC), gene copy number (n = 97) by fluorescent in situ hybridization (FISH), and mutation analysis by sequencing (n = 126). Fifty-nine percent of the samples were positive by IHC, 40% were positive by FISH, and 13.5% contained activating kinase domain mutations. Thirty-four percent of the FISH-positive and 27% of the mutant samples were also IHC-negative. All EGFR mutant patients had major clinical responses (five complete response and five partial response) to gefitinib or erlotinib treatment, although three of these tumors were IHC-negative and four were FISH-negative. In a retrospective analysis of samples from nine patients with excellent therapeutic responses (three complete response, five partial response, one stable disease) to erlotinib or gefitinib, mutations were identified in eight cases, but IHC was negative in four of these tumors. These results indicate that molecular diagnostic methods appear to be most important for the identification of lung adenocarcinoma patients who may benefit from EGFR inhibitor treatments.

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalJournal of Molecular Diagnostics
Volume10
Issue number2
DOIs
Publication statusPublished - Mar 2008

ASJC Scopus subject areas

  • Molecular Biology

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