Research & Education

ALK IHC Shown to Be Sensitive and Accurate in NSCLC

Findings Support Algorithmic Use of Test in Evaluation of NSCLC
April 22, 2014

Contact: Rob Mansheim
IASLC Director of Communications
(720) 325-2952

DENVER – A new study shows that immunohistochemical (IHC) analysis is sensitive, specific, and accurate for detecting ALK protein expression based on gene rearrangement in non-small cell lung cancer (NSCLC). The findings support the use of ALK IHC, which is more widely available and cost-effective than break-apart fluorescent in situ hybridization (FISH), which is currently the only approved ALK testing method for NSCLC.

Previous studies have indicated that ALK IHC, under the appropriate conditions, is sensitive and specific for determination of ALK protein expression based on gene rearrangement. However, a standardized ALK IHC diagnostic test is needed, as studies comparing IHC with FISH have used different ALK antibody clones, detection systems, antigen retrieval techniques, and scoring methods.

Fred R. Hirsch, MD, PhD, of the University of Colorado, led an international team of expert pathologists to evaluate the scoring of a new automated standardized ALK IHC assay with the antibody clone D5F3, an ultrasensitive detection system, an interpretation guide, and scoring method. The detection system involves an extra amplification step that has been shown to improve visualization of low-level ALK protein expression found in NSCLC compared with the same antibody clone and detection system without amplification.

Evaluating 100 NSCLC specimens that had been previously tested with break-apart FISH, the investigators found the ALK IHC assay to be highly sensitive (90%), specific (95%), and accurate (93%) relative to the ALK FISH results. There was agreement among seven of seven and six of seven readers on 88% and 96% of the cases before review, respectively, and agreement among seven of seven and six of seven readers on 95% and 97% of the cases after review, respectively. A majority score of multiple readers did not improve these results over an individual reader’s score. The findings of the study are published in the May issue of the Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer (IASLC).

"ALK IHC is a practical cost-effective alternative to the ALK FISH assay. In fact, there are even potential clinical benefits in some patients to ALK IHC over FISH, as demonstrated by significant clinical improvement with use of the ALK inhibitor crizotinib in patients who have tumors that were positive on ALK IHC testing but negative on ALK FISH testing," says Dr. Hirsch, who is also the CEO of IASLC. Coauthors of the study include IASLC members Murry W. Wynes, PhD; Ming S. Tsao; and Yasushi Yatabe.


About the IASLC:

The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association’s membership includes more than 3,800 lung cancer specialists in 80 countries. To learn more about IASLC please visit