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IASLC ATLAS OF ALK TESTING IN LUNG CANCER
The staining may appear heterogeneous in some tumors, particularly in surgical specimens (Figure 10); however, if preanalytic conditions are controlled for, the vast majority of tumor cells are stained, paralleling the homogeneous distribution of the ALK gene rearrangement in FISH analysis. The heterogeneity is likely related to heterogeneity of the fixation and does not seem to be related to the presence of a different histologic pattern. The sensitivity of ALK protein to delay of fixation is not an issue for biopsy specimens, but may be an issue when using tissue microarrays for screening of ALK in archived specimens. The paranuclear dot-like pattern reported as typical of the KIF5B-ALK rearrangement may require further confirmation (Figure 11) (Takeuchi 2009).
Figure 10. An example of heterogeneous positive staining in an ALK-positive tumor. The boxes in the left panel correspond to the images on the right. Signet ring cell carcinoma component is a potential pitfall for negative staining.
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Figure 11. Unusual positive reactions on IHC of a KIF5B-ALK-positive adenocarcinoma, showing a strong Golgi area-highlighted staining pattern (A: H & E staining, B: ALK staining) and a perinuclear halo pattern (C: H & E staining, D: ALK staining). The bars = 100 ?m. Reprinted from Takeuchi K, et al. KIF5B-ALK, a novel fusion oncokinase identified by an IHC-based diagnostic system for ALKpositive lung cancer. Clin Cancer Res. 2009;15:3143-3149.