ALK-Rearranged Adenosquamous Lung Cancer Presenting as Squamous Cell Carcinoma: A Potential Challenge to Histologic Type Triaging of NSCLC Biopsies for Molecular Studies

Dragnev, Konstantin H.; Gehr, Gerald; Memoli, Vincent A.; Tafe, Laura J.

doi:10.1016/j.cllc.2014.01.003

Cited by 14 publications

(17 citation statements)

References 17 publications

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“…Detailed FISH analysis revealed that cells harbouring ALK and ROS1 rearrangements were present in both AC and SCC components. ALKrearranged ASC has been described in two single case reports 15,30 and a few series. 7,31 Additionally, ROS1rearranged ASC, as observed in this study, was reported previously in a series analysis of NSCLCs harbouring ROS1 rearrangements.…”

Section: Discussionmentioning

confidence: 99%

“…Although there have been few large‐scale studies of driver gene alterations in ASC as represented by EGFR mutations, the prevalence of EGFR and KRAS mutations in ASC has been reported to be 13–44% and 4–13%, respectively. There have been only few reports of ALK gene rearrangement and two cases of ROS1 gene rearrangement in ASC …”

Section: Introductionmentioning

confidence: 99%

“…Although there have been few large-scale studies of driver gene alterations in ASC as represented by EGFR mutations, the prevalence of EGFR and KRAS mutations in ASC has been reported to be 13-44% and 4-13%, [5][6][7][8][9][10][11][12][13] respectively. There have been only few reports of ALK gene rearrangement 7,14,15 and two cases of ROS1 gene rearrangement in ASC. 16,17 Biomarkers of resistance to conventional cytotoxic agents in NSCLC include excision repair cross-completing 1 (ERCC1) and breast cancer susceptibility gene 1 (BRCA1), markers of resistance to platinumbased drugs; class III b tubulin (b III-tubulin), a marker of resistance to taxanes or vinorelbine; thymidylate synthase (TS), a marker of resistance to pemetrexed; and ribonucleotide reductase M1 polypeptide (RRM1), a marker of resistance to gemcitabine.…”

Section: Introductionmentioning

confidence: 99%

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Biomarker expression and druggable gene alterations for development of an appropriate therapeutic protocol for pulmonary adenosquamous carcinoma

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biomarker expression and druggable gene alterations for development of an appropriate therapeutic protocol for pulmonary adenosquamous carcinoma

et al. 2015

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“…However, ALK rearrangements have been found in older patients and smokers (34), squamous cell and adenosquamous carcinoma cases (35, 36), and rarely, patients with mutations in EGFR , Kirsten rat sarcoma viral oncogene homolog ( KRAS ), and B-Raf proto-oncogene, serine/threonine kinase ( BRAF ) (20 –22, 37, 38). Although the triage of samples based on clinicopathological features does increase the success rate of detection of ALK rearrangements (33), it is not an optimal strategy, since a portion of patients who could benefit from ALK inhibitors would unavoidably be excluded (4, 39, 40).…”

Section: Discussionmentioning

confidence: 99%

Quantification of Anaplastic Lymphoma Kinase Protein Expression in Non–Small Cell Lung Cancer Tissues from Patients Treated with Crizotinib

et al. 2016

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BACKGROUND Crizotinib has antitumor activity in ALK (anaplastic lymphoma receptor tyrosine kinase)-rearranged non–small cell lung cancer (NSCLC). The current diagnostic test for ALK rearrangement is breakapart fluorescence in situ hybridization (FISH), but FISH has low throughput and is not always reflective of protein concentrations. The emergence of multiple clinically relevant biomarkers in NSCLC necessitates efficient testing of scarce tissue samples. We developed an anaplastic lymphoma kinase (ALK) protein assay that uses multiplexed selected reaction monitoring (SRM) to quantify absolute amounts of ALK in formalin-fixed paraffin-embedded (FFPE) tumor tissue. METHODS After validation in formalin-fixed cell lines, the SRM assay was used to quantify concentrations of ALK in 18 FFPE NSCLC samples that had been tested for ALK by FISH and immunohistochemistry. Results were correlated with patient response to crizotinib. RESULTS We detected ALK in 11 of 14 NSCLC samples with known ALK rearrangements by FISH. Absolute ALK concentrations correlated with clinical response in 5 of 8 patients treated with crizotinib. The SRM assay did not detect ALK in 3 FISH-positive patients who had not responded to crizotinib. In 1 of these cases, DNA sequencing revealed a point mutation that predicts a nonfunctional ALK fusion protein. The SRM assay did not detect ALK in any tumor tissue with a negative ALK status by FISH or immunohistochemistry. CONCLUSIONS ALK concentrations measured by SRM correlate with crizotinib response in NSCLC patients. The ALK SRM proteomic assay, which may be multiplexed with other clinically relevant proteins, allows for rapid identification of patients potentially eligible for targeted therapies.

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“…and Chaft et al . reported adenosquamous carcinoma masquerading as pure squamous carcinoma with ALK rearrangement , . These studies illustrated that biopsies might represent an incomplete sampling of these complex tumors.…”

Section: Disscusionmentioning

confidence: 95%

Response to crizotinib in a squamous cell lung carcinoma patient harbouring echinoderm microtubule‐associated protein‐like 4‐anaplastic lymphoma translocation: A case report

2015

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Squamous cell lung cancer (SCC) presenting with anaplastic lymphoma kinase (ALK) translocation is rare. We present a case of ALK gene translocation‐SCC in which a remarkable tumor response to crizotinib was achieved after the failure of prior chemoradiotherapy. Considering this remarkable response, we conclude that ALK testing in female non‐smokers or in any patient unresponsive to the initial regimen of chemotherapy, is recommended for SCC patients.

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ALK-Rearranged Adenosquamous Lung Cancer Presenting as Squamous Cell Carcinoma: A Potential Challenge to Histologic Type Triaging of NSCLC Biopsies for Molecular Studies

Cited by 14 publications

References 17 publications

Biomarker expression and druggable gene alterations for development of an appropriate therapeutic protocol for pulmonary adenosquamous carcinoma

Biomarker expression and druggable gene alterations for development of an appropriate therapeutic protocol for pulmonary adenosquamous carcinoma

Quantification of Anaplastic Lymphoma Kinase Protein Expression in Non–Small Cell Lung Cancer Tissues from Patients Treated with Crizotinib

Response to crizotinib in a squamous cell lung carcinoma patient harbouring echinoderm microtubule‐associated protein‐like 4‐anaplastic lymphoma translocation: A case report

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