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J Thorac Oncol. 2012 Feb;7(2):348-54. doi: 10.1097/JTO.0b013e3182381535.

Dual IHC and FISH testing for ALK gene rearrangement in lung adenocarcinomas in a routine practice: a French study.

Author information

1
Plateforme hospitalière de Génétique Moléculaire des Cancers, Department of Hematology, Onco-Genetics and Immunology, Päle de Biologie et de Pathologie, CHU A Michallon, Grenoble, France. aflorin@chu-grenoble.fr

Abstract

INTRODUCTION:

In 2011, the French National Cancer Institute recommended ALK-fluorescence in situ hybridization (FISH) testing in all EGFR/KRAS-negative adenocarcinomas by all the hospital molecular genetics platforms of cancers; however, this technique remains time and cost consuming and not suitable for a large-scale screening, in contrast to immunohistochemistry (IHC).

METHODS:

To evaluate IHC as a prescreening tool, 441 specimens, including small biopsies and surgical specimens, were analyzed prospectively on the Grenoble molecular genetics platform. EGFR and KRAS mutation analyses and ALK IHC, using the 5A4 mAb on an automated staining module, were performed on all specimens; 100 were tested by both ALK IHC and FISH (break-apart probe).

RESULTS:

Twenty-seven cases out of 441 were strongly positive (3+ intensity in more than 60% of cells) with ALK mAb, two additional cases exhibited a faint staining (1+) in less than 30% of the cells. Among the 100 cases analyzed by IHC and FISH, 19 were not interpretable by FISH, but 21 were positive with both techniques. Sensitivity and specificity of IHC when compared with FISH were 95 and 100%, respectively. Eleven patients were included in crizotinib trials. Among the 352 analyzable specimens for mutations, 7% were EGFR and 29% were KRAS mutated.

CONCLUSIONS:

Our IHC protocol, using a commercially available antibody and an amplification step on an automated staining module, led to intense cytoplasmic staining in 6.5% of the adenocarcinomas screened. Our results favor ALK IHC prescreening on a daily routine on surgical specimens and on small biopsies before FISH testing.

PMID:
22071784
DOI:
10.1097/JTO.0b013e3182381535
[Indexed for MEDLINE]
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