In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 8100-8100
Abstract:
8100 Background: ALK rearrangements occur in nearly 5% of NSCLC and lead to a permanent ALK protein activation, targeted by a small molecule, the crizotinib. To date, FISH (Fluorescent In situ Hybridization) is considered as the gold standard to identify ALK abnormalities, but dual testing and pre-screening by immunohistochemistry have been proposed. Methods: The purpose of the study was to compare immunohistochemistry (IHC) using 5A4 and D5F3 Abs, with FISH and quantitative RT-PCR in a series of 500 surgical specimens, collected within one year from 15 French Thoracic Pathology Departments and INCa genetic platforms. Our study was deliberately enriched in ALK positive cases and clinicopathological data were recorded. Results: Among the 459 cases included to date, 340 were both FISH and IHC ALK negative, and 85 were ALK FISH and IHC positive. Fifteen cases were FISH neg/IHC pos, but with low staining scores; 12 cases were FISH pos/IHC neg, most provided by two centers. Seven cases were non interpretable by FISH, but 5 were ALK IHC positive. Regarding RTqPCR, nearly 50% of ALK positive cases presented a variant 1, 30% a variant 3a/b, and less than 5%, variants 2 or 7; 20%were negative or non interpretable. Discordant cases will be further discussed according to the crizotinib response. ALK positive patients were more frequently women (65 vs 42%) and younger than ALK negative patients (mean age 59 vs 64yrs); 72% were non or light smokers, whereas 75% of ALK negative patients were smokers (mean of 41PY). Histologically, most ALK positive and negative tumors presented a solid or acinar predominant architecture and were P63 negative. However, ALK positive tumors were more frequently TTF1 positive (91 vs 76%). Conclusions: 5A4 or D5F3 immunohistochemistry is a reliable and easy technique for routine diagnosis of ALK abnormalities, while FISH and RT-qPCR still dependent on pre-analytic conditions and technical expertise. However, in case of a suggestive clinical presentation, double testing with FISH remains the safer testing option as false negative IHC cases exist.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.8100
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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