Abstract
BackgroundAnaplastic lymphoma kinase (ALK) gene rearrangement is detected in 3 % to 13 % of non-small cell lung carcinoma patients, and these patients benefit from ALK inhibitors. The aim of this study was to determine the prevalence, the clinical and histological characteristics and the treatment outcomes of ALK-rearranged lung adenocarcinoma using immunohistochemistry (IHC) IHC, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) methodologies.MethodsA total of 268 pulmonary adenocarcinoma patients were screened for ALK expression by ALK IHC, which was confirmed by FISH and/or RT-PCR for ALK gene rearrangement. The treatment outcomes of ALK-rearranged patients were retrospectively reviewed.ResultsALK gene rearrangement was identified in 26 cases (9.7 %) with no EGFR co-mutation, and it showed significant associations with younger age, female sex and non-smoker status (p < 0.05). A cribriform growth pattern was identified as the dominant histologic feature, and a solid signet ring cell component was focally present in a minority of the cases. Among 12 ALK-rearranged patients with conventional treatment, seven cases in the early stage of disease were cured and alive, and five patients in the late stage of the disease progressed and died, with a median overall survival (OS) at 14 months. Of the 14 patients receiving crizotinib, all of them had clinical benefit from crizotinib treatment, with one patient having a complete response (CR), 12 patients having a partial response (PR) and one patient having stable disease (SD). On the cutoff date, six of 14 patients were continuing crizotinib treatment with a median time of response of 7.5 (3–13) months, while eight patients had disease progression, and five of them died with a median OS at 8 months.ConclusionALK gene rearrangement tended to occur in younger, non-smoking, female patients. ALK IHC is a reliable screening method to detect ALK gene rearrangement. Crizotinib therapy provided treatment benefit in ALK-rearranged adenocarcinoma patients especially in advanced stages of the disease.
Highlights
Anaplastic lymphoma kinase (ALK) gene rearrangement is detected in 3 % to 13 % of non-small cell lung carcinoma patients, and these patients benefit from ALK inhibitors
Among the 268 patients, 26 (9.7 %) cases were ALKpositive after being screened by IHC and confirmed by fluorescence in situ hybridization (FISH) and RTPCR
ALK rearrangement was detected in 3-13 % of Non-small cell lung cancer (NSCLC) patients, and this occurrence was associated with younger age, non-smoking, advanced stage disease and the presence of signet ring cell morphology [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]
Summary
Anaplastic lymphoma kinase (ALK) gene rearrangement is detected in 3 % to 13 % of non-small cell lung carcinoma patients, and these patients benefit from ALK inhibitors. Novel fusion genes, including anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated proteinlike 4 (EML4) on chromosome 2 or ALK with other partner genes, have been observed [7,8,9,10] This ALK gene rearrangement has been identified in 3-13 % of NSCLC patients and is significantly associated with young, female, non-smoking patients and with adenocarcinoma subtype with solid signet ring cell features and advanced stage of disease [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]. Ceritinib and alectinib are second-generation ALK inhibitors that are already approved by the US FDA and Japan FDA, respectively [41, 42]
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