In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e21117-e21117
Abstract:
e21117 Background: Activating mutations in the tyrosine kinase domain of the EGFR gene in lung carcinoma has been associated with a dramatic response to tyrosine kinase inhibitors. Therefore, routine analysis of pathological specimens is mandatory in clinical practice to predict patient response. We have analyzed the results of the tests we performed during years 2010 and 2011. Methods: DNA was extracted from formalin-fixed paraffin-embedded tissues, following macrodisection, using an iPrep robot (Invitrogen). The p.L858R and p.L861Q substitutions (exon 21) were assessed by allele-specific PCR and exon 19 deletions by PCR amplification followed by DNA fragment analysis (polyacrylamide gel electrophoresis). These techniques allowed us to detect these mutations when present in at least 2% of the cells. Results: During these 2 years, we analyzed samples from 1,041 patients (including 907 adenocarcinomas, 71 large cell carcinomas and 28 squamous cell carcinomas). The EGFR mutational status could not be determined in 51 cases : DNA could not be amplified in 23 cases (2.2%), and 28 samples (2.7%) contained a limited percentage ( 〈 10%) of cancer cells. The EGFR status could thus be successfully determined in 990 (95.1%) samples. EGFR mutations were detected in 142 (14.3%) patients : 74 exon 19 deletions, and 68 p.L858R mutation. The mutation rate was, as expected, higher in women (24.0%) than in men (7.2%), and mutated patients were significantly older than non mutated patients (median age : 71 y vs 63 y). Furthermore, the mutation rate was much higher in tumors expressing the TTF-1 antigen (117/638; 18.3%) than in TTF-1 negative tumors (5/228; 2.2%). Similar mutation rates were obtained with primary tumors (89/661; 13.5%) and metastases (40/274; 14.6%), and with surgical specimen (43/325; 13.2%), fiberoptic bronchial biopsies (36/250; 14.4%), CT-guided needle biopsies (25/181; 13.8%) and transbronchial needle aspirates (5/38; 13.2%). Conclusions: The results obtained through routine analysis of more than 1000 samples indicated that our procedure is very efficient. All types of samples can be analyzed without any significant bias. TTF-1 immunostaining might be used to predict for negative EGFR mutation status.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e21117
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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