PT  - JOURNAL ARTICLE
AU  - Ragazzi, Moira
AU  - Tamagnini, Ione
AU  - Bisagni, Alessandra
AU  - Cavazza, Alberto
AU  - Pagano, Maria
AU  - Baldi, Licia
AU  - Boni, Corrado
AU  - Cantile, Flavia
AU  - Barbieri, Fausto
AU  - Nicoli, Davide
AU  - Sartori, Giuliana
AU  - de Biase, Dario
AU  - Gardini, Giorgio
AU  - Rossi, Giulio
TI  - Diamond: immunohistochemistry versus sequencing in <em>EGFR</em> analysis of lung adenocarcinomas
AID  - 10.1136/jclinpath-2015-203348
DP  - 2016 May 01
TA  - Journal of Clinical Pathology
PG  - 440--447
VI  - 69
IP  - 5
4099  - http://jcp.bmj.com/content/69/5/440.short
4100  - http://jcp.bmj.com/content/69/5/440.full
SO  - J Clin Pathol2016 May 01; 69
AB  - Aims Identification of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas is the single most important predictor of clinical response and outcome using EGFR tyrosine kinase inhibitors (TKIs). EGFR E746-A750del and L858R mutations are the most common gene alterations, also predicting the best clinical response to TKIs. We evaluated the accuracy of EGFR mutation-specific antibodies in a large cohort of lung adenocarcinomas, with different molecular settings and types of tissue samples.Methods 300 lung adenocarcinomas diagnosed on cytology (48 cell blocks), biopsy (157 cases) and surgical resections (95 cases) were selected. All cases were investigated for EGFR by sequencing and two mutation-specific antibodies (clone 6B6 for E746-A750del; clone 43B2 for L858R) were tested using an automated immunostainer. Discordant results were investigated by next-generation sequencing (NGS).Results Overall sensitivity and specificity of mutant-specific antibodies were 58.6% and 98.0%, respectively, and they increased up to 84% and 100% if only tumours harbouring E746-A750del were considered. In 13 discordant cases, NGS confirmed immunohistochemistry results in eight samples.Conclusions The EGFR mutation-specific antibodies have a fair/good sensitivity and good/high specificity in identifying classic mutations, but they cannot replace molecular tests. The antibodies work equally well on biopsies and cell blocks, possibly permitting a rapid screening in cases with poor material.