Can we eliminate squamous cell carcinoma of the lung from testing of EML4-ALK fusion gene?

ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare

“…Based on these clinicopathologic characteristics, current recommendations for ALK molecular testing should be used to select patients for ALK-targeted TKI therapy within advanced, non-squamous NSCLC. However, tumors with squamous cell carcinoma or adenosquamous histologies, albeit at a lower frequency (∼1%) than adenocarcinomas, have been reported to carry ALK translocations [6,26,28,32,35,[40][41][42][43]. Based on the NanoString fusion panel, we have examined a total of 282 cases of lung SCC combining the 214 from this study and the 68 from the published results of Fang et al [32].…”

ALK/EML4 Fusion Gene May Be Found in Pure Squamous Carcinoma of the Lung

“…Doubts have been cast on reports showing ALK rearrangements in squamous lung cancers, as those might represent adenosquamous neoplasms misdiagnosed because of false squamous cell differentiation, biopsy sample not representative of the entire tumor, and lack of use of an immunohistochemical confirmatory panel. [2][3][4]7 Consequently, it is common belief that the true prevalence of ALK translocations in pure squamous cell lung carcinoma approaches zero. Our study on a series of 40 consecutive cases diagnosed as pure squamous cell carcinoma upon extensive sampling of the entire surgical specimens and confirmed by the typical immunophenotypical positivity for ∆n-p63 and CK5/6 and negativity for Napsin-A, TTF-1 and CK7, revealed that one case (2.5%) harbored an EML4-ALK fusion gene.…”

“…1 However, the report of cases of lung squamous cell cancers harboring ALK gene rearrangements 2,3 has raised the question whether this histologic subtype should be also evaluated for such molecular predictive test. 4 The doubt exists that these cases could be adenosquamous carcinomas misdiagnosed as squamous cell carcinomas because of either limited sampling of surgically removed lesions or bioptic samples that were not representative of the entire lesion. 5,6 As the presence of ALK rearrangement might offer a therapeutical option for patients affected by squamous cell carcinoma of the lung, we sought to assess its prevalence in a series of 40 consecutive bona fide squamous cell lung carcinomas observed at our institution.…”

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

“…Notably, the vast majority of ALK gene rearrangements were observed in lung adenocarcinoma specimens. The incidence of ALK gene rearrangements in lung SqCC has not been well documented except few cases were reported [ 29 , 30 ]. In the present study, we carried out an immunohistochemical staining in 207 cases of consecutive lung SqCC patients with a VENTANA anti-ALK (D5F3) specific rabbit monoclonal antibody.…”