Figure 1.
Fluorescent in situ hybridization (FISH) assay for ALK using dual-color break-apart probe.
Distinct red (thick arrow) and green (thin arrow) break apart signals indicate the ALK rearrangement, and a fusion signal (arrow head) represents wild-type ALK gene.
Table 1.
Comparison of clinicopathological characteristics of the patients between the test and validation set.
Figure 2.
Histological features of ALK-positive and ALK-negative adenocarcinomas on H&E stain (A, B, C, D) and on ALK immunostaining by the iAEP method (E, F, G, H).
P3 and P7 (A and B, respectively), adenocarcinomas with mucinous cribriform pattern, showed iScore 3 (E and F, respectively); N1 (C), squamous cell carcinoma showed iScore 1 (G); N3 (D), small cell carcinoma showed iScore 2 (H).
Figure 3.
The results of assessment for ALK rearrangement in the test and validation set.
Table 2.
Correlation of the results between ALK IHC and FISH in all patients.
Table 3.
Clinicopathological characteristics of adenocarcinoma according to ALK rearrangement status.
Table 4.
Characteristics of patients with ALK true and false positive tumors.
Figure 4.
Diagnostic algorithm for the identification of ALK rearrangement in lung cancer.
For cases with iScore 3 or 0, confirmatory FISH or RT-PCR can be skipped. However, if a case with non-adenocarcinoma is judged iScore 3, a confirmatory test should be done. Lung cancers without ALK rearrangement sometimes show positivity in highly-sensitive anti-ALK IHC, like iAEP, especially in cases with neuroendocrine differentiation (small-cell, large-cell neuroendocrine, and other carcinomas with focally neuroendocrine differentiation).