Table 4.
Summary of published articles comparing ALK analysis by FISH and IHC
| Reference | Antibody | Source | Detection method | Samples, n | ALK+ | ALK− | Comments | ||
|---|---|---|---|---|---|---|---|---|---|
| FISH | IHC | FISH | IHC | ||||||
| Shaw et al. [25] | ALK1 | Dako | n.a. | NSCLC, 141 | 19 (13 %) | 19 (13 %) | n.a. | n.a. | Only FISH+ cases were confirmed with IHC |
| Boland et al. [44] | ALK1 | Dako | n.a. | NSCLC, 335 | 6 (1.8 %) | 6 (1.8 %) | n.a. | n.a. | The 6 cases testing positive using IHC were positive with FISH. 8 of the IHC ALK− cases were also tested using FISH. All were negative |
| Rodig et al. [24] | ALK1 | Dako | EnVision+ | Adeno, 358 | 20 (5.6 %) | n.a. | n.a. | n.a. | 8 of the 10 FISH ALK+ cases with sufficient tissue were also IHC ALK+ (sensitivity = 80 %); 1 case ALK– by FISH was ALK+ by IHC |
| Mino-Kenudson et al. [49] | ALK1 | Dako | EnVision+ | Adeno, 153 | 22 (14.3 %) | n.a. | n.a. | n.a. | Sensitivity and specificity of IHC were 67 and 97 %, respectively |
| D5F3 | Cell ST | EnVision+ | Adeno, 153 | 22 (14.3 %) | n.a. | n.a. | n.a. | Sensitivity and specificity of IHC were 100 and 99 %, respectively | |
| Yi et al. [46] | ALK1 | Dako | Advance | Adeno, 101 | 10 (9.9 %) | 11a (10.9 %) | 91 (90.1 %) | 90a (89.1 %) | Of the 10 FISH+ cases, 8 were IHC 3+, 1 was IHC 2+ and 1 was IHC +; of the 91 FISH– cases, 2 were IHC 2+, 20 were IHC 1+, 69 were IHC 0; sensitivity and specificitya of IHC were 90 and 97.8 %, respectively |
| Paik et al. [47] | 5A4 | Novocastra | i-view | NSCLC, 453 | 19 (4.2 %)a | 26 (5.7 %) | 434 (95.8 %) | 427a (94.3 %) | Of the 19 FISH+ cases, 16 were IHC 3+, 3 were IHC 2+; of the 434 FISH− cases, 7 were IHC 2+, 14 were IHC 1+, 413 were IHC 0; sensitivity and specificitya of IHC were 100 and 92.5 %, respectively |
| Mitsudomi et al. [64] | 5A4 | Santa Cruz | EnVision+ | NSCLC, 345 | n.a. | 12 (3.5 %) | n.a. | n.a. | All these 12 IHC ALK+ cases were also FISH ALK+; all IHC ALK– cases were also FISH ALK– |
| Martinez et al. [65] | D5F3 | Cell ST | n.a. | NSCLC, 71 | 6 (8.5 %) | n.a. | n.a. | n.a. | All FISH ALK– negative cases were also IHC ALK–. 4/6 FISH ALK+ cases were also ALK IHC+; 1 case was IHC ALK–; 1 sample could not be analysed. |
| Paik et al. [66] | 5A4 | Novocastra | n.a. | NSCLC, 735 | 28 (3.8 %) | 35 (4.8 %) | 707 (96.2 %) | 700 (95.2 %) | Of all cases, 15 were IHC 3+, 20 were IHC 2+, 20 IHC 1+, 700 were IHC0; all IHC0/1+ were ALK FISH–, all IHC 3+ cases were ALK FISH+, and 13 of the 20 IHC 2+ were FISH+; sensitivity and specificitya of IHC were 100 and 96.2 %, respectively |
| Adeno, 395 | 27 (6.8 %) | n.a. | 368 (93.2 %) | n.a. | |||||
| McLeer-Florin et al. [48] | 5A4 | Abcam | i-view | Adeno, 441 | n.a. | 29 (6.5 %) | n.a. | n.a. | Of 81 cases with interpretable IHC and FISH results, 21 were FISH ALK+; of these 21 cases, 19 were IHC ALK+ and 2 were IHC doubtfully positive; of the 60 FISH ALK– cases, 1 was IHC ALK+ and 59 were IHC ALK– |
| Yang et al. [43] | ALK1 | Dako | Advance | Adeno, 300 | 22/216 (10.2 %) | 32 (10.7 %)a | 194/216 (89.8 %) | 268 (89.3 %) | All IHC 0 cases were FISH ALK– and all IHC 3+ were FISH ALK+; 96.9 % of IHC 1+ cases were FISH ALK− and 85.7 % of IHC 2+ cases were FISH ALK+ |
IHC scores of 0 and 1+ are regarded as negative; scores of 2+ or 3+ as positive
Adeno adenocarcinomas, ALK anaplastic large cell kinase, FISH fluorescence in situ hybridization, IHC immunohistochemistry, n.a. not available, NSCLC non-small cell lung cancer, ALK+/– positive/negative results for ALK rearrangement
aUsing FISH as the gold standard