Figure 1.
Anaplastic lymphoma kinase (ALK) immunohistochemistry (IHC) staining using D5F3 antibody with Dako EnVision detection kit and fluorescence in situ hybridization(FISH) using Vysis LSI ALK probe in lung adenocarcinoma.
(A) IHC score 3+ for strong, granular cytoplasmic staining in most of tumor cells, at least more than 75% tumor cells, diffusely homogeneity in distribution. (B) IHC score 2+(borderline or equivocal staining) for moderate, smooth cytoplasmic staining(also can partly present strong staining) in most of tumor cells, at least more than 50% tumor cells; (C) IHC score 1+ for faint, focal cytoplasmic staining less than 2+ criteria; and (D) IHC score 0 for completely no staining. (E) FISH-positive cases representing split signals and/or deleted green signals (DGS). (F) FISH-negative case showing intact two fused signals per nucleus. The pleural effusion cell block of case #223, of which bronchial biopsy tissue presented as IHC 3+ and FISH negative, showed IHC3+ in all tumor cells (G) and FISH positive (F) (percentage of positive cells, 94%, all positive cells characterized by DGS). Original magnification ×200 (A,B,C,D,G), ×1000 (E,F,H).
Table 1.
Relationship between ALK IHC and FISH in the unselected 368 lung adenocarcinomas analysis.
Table 2.
Three discrepant cases which had ALK IHC3+ and FISH “negative” results.
Figure 2.
Patterns proportions of split signal pattern as positive cell, deleted green signal (DGS) pattern as positive cell, and negative cell of each case detected by FISH in ALK IHC 3+ group (A) and 2+ group (B).
Table 3.
Relationship between ALK status and clinic, EGFR characteristics in the unselected 368 lung adenocarcinomas.
Figure 3.
Diagnostic algorithm that uses immunohistochemistry (IHC) as the primary test for identification anaplastic lymphoma kinase (ALK) positive in lung adenocarcinoma.
Dot lines correspond to that we also recommend initial ALK testing practice begins with IHC and fluorescence in situ hybridization (FISH) combined test, which would help be familiar with the relation of the IHC semiquantitatively score and FISH. aTTF-1, thyroid transcription factor-1; bPC%, percentage of positive cells; cfailed, no interpretable, or limited tissue; dEGFR, epidermal growth factor receptor.