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. 2014 Dec 21;33(1):109.
doi: 10.1186/s13046-014-0109-2.

Detection of ALK protein expression in lung squamous cell carcinomas by immunohistochemistry

Jiandong Wang  1 , Qin Shen  1 , Qunli Shi  2 , Bo Yu  3 , Xuan Wang  4 , Kai Cheng  5 , Guangming Lu  6 , Xiaojun Zhou  7
Affiliations

Detection of ALK protein expression in lung squamous cell carcinomas by immunohistochemistry

Jiandong Wang et al. J Exp Clin Cancer Res. .

Abstract

Background: The echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene rearrangements occur in approximately 5% of lung adenocarcimomas (ACA), leading to ALK overexpression and predicting response to targeted therapy. To the present, few studies have been focused on the expression of ALK protein in lung squamous cell carcinomas (SqCC). Only several cases of lung SqCC were reported expression of ALK protein. No clinical study has been published to explicit the relationship between ALK expression and the response to targeted therapy in SqCC.

Methods: In this study, we analyzed ALK protein expression with a specific rabbit monoclonal Ig antibody (D5F3 clone) in 207 cases of lung SqCC. The positive cases were confirmed with ALK fluorescence in situ hybridization (FISH) and RT-PCR.

Results: We found that 3 out of 207 (1.4%) cases of lung SqCC were ALK positive detected by IHC staining, which were confirmed by ALK FISH and RT-PCR.

Conclusions: Our results indicate that ALK protein expression is not a rare molecular event in SqCC. Although the frequency of EML4-ALK rearrangements is lower in lung SqCC than that in lung adenocarcinomas, their presence may provide additional treatment options in lung SqCC. The response of SqCC patients with ALK expression to target therapy of crizotinib should be explored.

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Figures

Figure 1
Figure 1
Lung SqCC samples were diagnosed combining morphologic appearance and IHC staining including thyroid transcription factor-1 (TTF-1), transformation-related protein 63 (p63) and/or cytokeratin (CK5/6). A: Hematoxlin and eosin staining. B: IHC staining for p63. C: IHC staining for CK5/6. D: IHC staining for TTF-1. Original magnification, ×400.
Figure 2
Figure 2
Representative ALK IHC images. A: Negative. B: Weak expression. C: Moderate expression. D: Strong staining. Original magnification, ×400.
Figure 3
Figure 3
Dual-color, break-apart fluorescent in situ hybridization was performed to confirm the ALK expression. The centromeric (green) and telomeric (red) fland the ALK locus. Splitting of the red and green signals indicates ALK rearrangement. A: No EML4-ALK rearrangement. B, C and D: EML4-ALK rearrangements. A break-apart signal pattern, where one fusion signal and a single red and green signal pattern was observed in most nuclei (B and C). A few nuclei showed a predominant signal pattern of deletion of the 5’region (D).
See this image and copyright information in PMC

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