Effusion immunocytochemistry as an alternative approach for the selection of first-line targeted therapy in advanced lung adenocarcinoma
Journal
Journal of Thoracic Oncology
Journal Volume
7
Journal Issue
6
Pages
993-1000
Date Issued
2012
Author(s)
Tsai M.-F.
Wei P.-F.
Abstract
Introduction: Tumor tissue is often not obtainable or suitable for molecular-based epidermal growth factor receptor (EGFR) mutational analysis in advanced non-small-cell lung cancer (NSCLC). This retrospective and single-institution study was conducted to evaluate the role of effusion immunocytochemistry using two EGFR mutant-specific antibodies for the detection of relevant EGFR mutations in NSCLC, along with the selection of candidates for first-line therapy with EGFR tyrosine kinase inhibitors (TKIs). METHODS: Immunocytochemistry using two antibodies binding specifically to the major forms of mutant EGFR, L858R, and E746-A750 deletion (delE746-A750), was performed on cell blocks of malignant pleural effusion (MPE) from 78 patients with lung adenocarcinoma, who received first-line EGFR TKIs. The yield of EGFR-mutation detection and prediction of response rate and progression-free survival to TKI treatment by immunocytochemistry were compared with those by clinical characteristics and EGFR sequencing using cell-derived RNA from MPEs. RESULTS: Of the 78 MPE samples, direct sequencing using cell-derived RNA identified L858R mutation in 42 cases, deletions in exon 19 in 12 cases (delE746-A750 in eight cases), other types of mutations in three cases, and wild-type EGFR in 21 cases. Effusion immunocytochemistry with these two mutant-specific antibodies exhibited a sensitivity of 71% and 88% and a specificity of 86% and 96% for identifying predefined L858R and delE746-A750 mutations, respectively. Effusion immunocytochemistry provided a superior prediction of tumor response and progression-free survival to first-line EGFR TKIs than did clinical characteristics like sex and smoking status. Patients whose effusion immunocytochemistry showed a reaction to either of the two antibodies had a comparable TKI response rate (67% versus 72%) to those with EGFR mutations assessed by direct sequencing from cell-derived RNA. CONCLUSIONS: Effusion immunocytochemistry could be introduced into clinical practice to identify more NSCLC patients likely to have benefit from first-line TKI treatment, especially for those without adequate tissue for molecular-based EGFR analysis. Copyright ? 2012 by the International Association for the Study of Lung Cancer.
SDGs
Other Subjects
epidermal growth factor receptor; erlotinib; gefitinib; adult; advanced cancer; aged; antibody combining site; article; clinical practice; controlled study; cytopathology; exocrine cell; exon; female; gene deletion; gene mutation; human; human cell; immunocytochemistry; immunohistochemistry; immunoreactivity; lung adenocarcinoma; lung non small cell cancer; major clinical study; male; overall survival; pleura effusion; predictive value; priority journal; progression free survival; retrospective study; sensitivity and specificity; sequence analysis; smoking; treatment response; wild type
Publisher
Lippincott Williams and Wilkins
Type
journal article