64
IASLC ATLAS OF ALK TESTING IN LUNG CANCER
Adenocarcinoma patients with available ALK IHC data N=1099
100
ALK IHC+ N=69
ALK IHC– N=1030
99.3%
93.5%
87.5%
9.5% 90.5%
80 60 40 20 0 6.5% IHC result 0+ IHC result 1+ 12.5% IHC result 2+
ALK IHC 1:2 Matched Cohort N=207 Matching factors in order of importance: stage, gender/smoking status, center/ year of surgery/age ALK IHC+ N=69* 38 FISH– 22 FISH+ ALK IHC– N=138 1 FISH+ 137 FISH–
Percent
IHC result 3+
FISH ALK
FISH Negative
FISH Positive
*9, FISH not done
Figure 1. Results from the ETOP Lungscape project. Among 1,099 lung adenocarcinomas, 69 were identified as ALK positive on IHC. Concordance between IHC and FISH was analyzed in a matched cohort (right).
of samples, and the ICC improved significantly (0.94). The ICC for FISH was 0.68, and, the sensitivity and specificity of FISH results across centers were 88% to 100% and 100%, respectively. The authors of this study concluded that standardization across multiple centers for ALK testing by IHC and FISH can be achieved; IHC detected all tumors that were ALK positive on FISH, except for one discrepant case with atypical FISH findings of unknown aberration and clinical implication. However, the results also suggest the potential occurrence of occasional false-negative results on FISH. Japan Crizotinib was approved by the Pharmaceutical and Medical Device Agency in Japan on March 30, 2012, but the agent could not be used in clinical practice until it was listed in the National Health Insurance Drug Price List. For 3 months before the drug was listed, Pfizer Japan conducted a prereimbursement program for ethical reasons, with the pharmaceutical company providing crizotinib to a registered institute when a tumor was determined to be ALK positive. In the program, FFPE samples were examined simultaneously with FISH (Vysis LSI ALK Break Apart FISH Probe Kit, Abbott Molecular) and IHC (the antibody clone 5A4 in conjunction with the EnVision FLEX+ system [Dako] and an iAEP detection kit [Nichirei Biosystems]), and RT-PCR was used on cytology samples, such as pleural effusion. A total of 5,514 tests were done: 2,630 on FISH, 2,631 on IHC, and 253 on RT-PCR. The test success rates were 93%, 96%, and 94%, respectively. Although concordance between FISH and IHC was 98%, the sensitivity of ALK IHC was limited to 86%. The results were positive on both FISH and IHC for 213 specimens; 36 specimens were positive on FISH but negative on IHC, and 12 specimens were negative on FISH but positive on IHC. The results were negative on both FISH and IHC for 2,076 specimens. Based on these results, the Japanese Lung Cancer Society added a special note to its 2011 ALK testing guidance stating that, even when a patient is deemed to be a good