Abstract
BackgroundThe 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.MethodsIn 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-014-0109-2) contains supplementary material, which is available to authorized users.
Highlights
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
Clinical samples Patients diagnosed with squamous cell lung carcinoma and the tumor specimens subjected to ALK protein expression analysis in Jinling Hospital, China, between 2010 and 2014 were included in this study (Additional file 1)
ALK fluorescence in situ hybridization (FISH) All cases of squamous cell carcinomas (SqCC) samples with expression of ALK were confirmed by ALK FISH
Summary
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. Few studies have been focused on the expression of ALK protein in lung squamous cell carcinomas (SqCC). No clinical study has been published to explicit the relationship between ALK expression and the response to targeted therapy in SqCC. NSCLCs represent a diverse entity that can be subclassified further into distinct histologic subtypes including adenocarcinoma, squamous cell carcinoma (SqCC), large cell carcinoma, large cell neuroendocrine carcinoma, anaplastic carcinoma, and giant cell carcinoma. NSCLCs represent approximately 80% of all lung cancer subtypes and it is the leading worldwide cause of cancer related death. Lung SqCC is a common type of NSCLCs, causing approximately 400,000 deaths per year worldwide. Most lung cancers are often diagnosed at advanced stages of the disease, and the mainstay of therapy is systemic chemotherapy, typically with a platinum-based regimen. Recent progress in understanding the biology of this tumor, characterization of NSCLC by molecular typing, in adenocarcinomas of the
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