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

Caliò, Anna; Nottegar, Alessia; Gilioli, Eliana; Bria, Emilio; Pilotto, Sara; Peretti, Umberto; Kinspergher, Stefania; Simionato, Francesca; Pedron, Serena; Knuutila, Sakari; Tortora, Giampaolo; Eccher, Albino; Santo, Antonio; Tondulli, Luca; Inghirami, Giorgio; Tabbò, Fabrizio; Martignoni, Guido; Chilosi, Marco; Scarpa, Aldo; Brunelli, Matteo

doi:10.1097/jto.0000000000000109

Cited by 51 publications

(44 citation statements)

References 15 publications

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“…The data are also supported by other studies specifically reporting the frequency of 0% ALK translocation in SCC patients [23][24][25]. Since the current practice guidelines recommend a molecular testing for lung adenocarcinoma or mixed lung cancer with an ADC component to select patients for targeted TKI therapy, reported cases of lung squamous cancer harboring gene rearrangements challenge the molecular diagnosis based on histologic subtypes [12,15,[26][27][28][29][30]. However, doubts have been cast on reports showing ALK and/or ROS1 rearrangements in squamous lung cancer, as the small biopsy specimens were not representative of the whole tumor characteristics, and an immunohistochemistry panel was not available to validate the squamous differentiation.…”

Section: Introductionmentioning

confidence: 49%

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

et al. 2016

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Section: Introductionmentioning

confidence: 49%

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

et al. 2016

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“…Among the 209 patients with squamous cell carcinomas, 16 incidences (7.7%) of ALK rearrangement were detected, which is less than the incidence (11.0%) in adenocarcinoma, but not significantly so. Caliò et al (2014) also demonstrated ALK rearrangements in squamous lung cancers, as those might represent adenosquamous neoplasms misdiagnosed because of false squamous cell carcinomas, limited biopsy samples not representative of the entire lesion, and lack of use of an immunohistochemical confirmatory panel. However, the 16 patients with squamous carcinoma enrolled in our study comprised nine with whole-tissue from surgery, demonstrating that the ALK translocation might be found in pure squamous carcinoma of the lung.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Lei

Wang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangements and epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been intensively studied. The objective of this study was to determine the clinicopathological characteristics in genotype-specific subsets of patients with NSCLC to help ensure the optimal identification of patients whose tumors harbor these two driver mutations. The incidence of ALK rearrangements was investigated in 763 NSCLC specimens by immunohistochemistry using a D5F3 antibody, and EGFR mutations were assessed by amplification refractory mutation system (ARMS) in 222 patients with lung adenocarcinoma. Of these, 73 (9.6%) were detected as being ALK-positive; this designation was associated with young age, female gender, never-smokers, lymph node metastasis, and poor tumor differentiation, but not with histology. EGFR mutations were identified in 102 (45.9%) of 222 adenocarcinoma samples, and were more frequent in females and never-smokers. No difference in age was observed. Specifically, we identified several cases of complex EGFR mutations, and concomitant EGFR mutations and ALK rearrangements. These results suggest that young women and never-smokers are at risk for ALK rearrangement. We also identified concomitant mutations of EGFR and rearrangements of ALK in this study.

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“…Clinical characteristics should not be a limiting factor for exploratory analyses, and testing should be particularly encouraged in the case of never/light smokers [28]. ALK abnormalities in epidermoid lung cancers are extremely rare (one (0.2%) out of 523) [28], and the few studies reporting higher incidences should not, at this stage, change the above recommendations about screening [29].…”

Section: Characteristics Of Alk + Populationsmentioning

confidence: 99%

Therapeutic management of ALK⁺nonsmall cell lung cancer patients

2015

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With therapeutic approaches based on oncogene addiction offering significant anticancer benefit, the identification of anaplastic lymphoma kinase (ALK) rearrangements is a key aspect of the management of lung cancers. The EML4-ALK gene fusion is detected in 4-8% of all lung cancers, predominantly in light smokers or nonsmokers. Crizotinib, the first agent to be approved in this indication, is associated with a median progression-free survival of 10.9 months when given as first-line treatment and 7.7 months when administered after chemotherapy. Median overall survival with crizotinib in the second-line setting is 20.3 months. Second-generation ALK inhibitors are currently being evaluated, with early studies giving impressive results, notably in patients resistant to crizotinib or with brain metastases. Among available chemotherapies, pemetrexed appears to be particularly active in this population. Despite this progress, several questions remain unanswered. What detection strategies should be favoured? What underlies the mechanisms of resistance and what options are available to overcome them? What are the best approaches for progressing patients? This review provides an overview of current data in the literature and addresses these questions. @ERSpublications ALK defines patients who benefit from ALK inhibitors so should be systematically tested in advanced nonsquamous NSCLC http://ow.ly/KQ2oSCopyright ©ERS 2015 This article has supplementary material available from

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

Abstract: ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.

Cited by 51 publications

References 15 publications

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

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

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Therapeutic management of ALK⁺nonsmall cell lung cancer patients

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

Abstract: ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.

Cited by 51 publications

References 15 publications

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

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

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Therapeutic management of ALK+nonsmall cell lung cancer patients

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Therapeutic management of ALK⁺nonsmall cell lung cancer patients