Optimized immunohistochemistry using the D5F3 antibody provides a reliable test for identification of ALK-positive lung adenocarcinomas

Abstract

We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC-positive/FISH-negative cases, one was unsuitable for FISH and three had abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were FISH-negative. The FISH positive/IHC-positive cases with moderately intense reactivity had the typical clinicopathologic features of ALK-positive patients (younger age, p < 0.01; higher frequency in metastatic sites, p < 0.01; cribriform/mucinous/signet histology, p < 0.01; stage IV disease, p < 0.01). In conclusion, our findings indicate that optimized IHC using the D5F3 antibody provides a reliable and inexpensive test for identification of ALK-positive adenocarcinomas. Inclusion of this information in the pathology report at the time of the histological diagnosis might significantly shorten time to treatment.

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