Common and Rare EGFR Mutations. The Challenge of Their Cytological Detection
Esther Diana Rossi, Rene Gerhard, Luis Cirnes, Jose C Machado, Fernando C Schmitt. Catholic University of Sacred Heart, Rome, Italy; IPATIMUP-Institute of Pathology and Immunology of Porto University, Porto, Portugal; Medical Faculty of the University of Porto, Porto, Portugal
Background: Lung cancer represents the third most common cancer and the first cause of cancer mortality.EGFR mutation is referred in about 30-40% of patients with lung adenocarcinoma or mixed squamous-adenocarcinoma type and is essential for therapeutic decision.EGFR mutations are located within exons18 to 21 of the kinase domain, mainly in-frame deletions in exon19 and/or point mutations in exon 21.The detection of rarer mutations in exons18 and 20 can be performed by direct sequencing even if the quantity of neoplastic cells,obtained for cytology,is rather limited. The objective of this study was to compare the rate of detection of EGFR mutations in cytological samples to that observed in histological samples.
Design: A total of 893 lung cancer patients(491 female and 402 male),with a median age of 52 y-old were studied for EGFR mutations using Sanger-sequencing.The cohort branched into 790 histological samples(small biopsies) and 103 cytological cases.The histological diagnoses were:457 adenocarcinomas, 407 non-small cell carcinoma and 29 squamous cell carcinomas.
Results: A total of 164(18.3%)mutations were found,including common mutations in exons 19 and 21 and rare mutations in exons 18 and 20.The common mutations were in-frame deletions of exon 19(88/164;53.6%)and substitutions in exon 21(56/164;34.1%).The rare mutations corresponded to substitutions in exon 18(7/164;4.2%) and other different mutations (including insertions, deletions and substitutions)in exon 20(13/164;7.9%).Table 1 summarizes the findings of EGFR mutations in the two types of samples and there is no statistically significant difference between the rates of detection of mutations in exon 19 and 21,and exon 18 and 20 in cytological and histological material(chi-square value:4.45;p-value:0.1079).
|EGFR-wild type||85 (82.5%)||644 (81.5%)|
|EGFR common mutations||13 (12.6%)||131 (16.5%)|
|EGFR rare mutations||5 (4.8%)||15 (1.8%)|