The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted TherapyReport as inadecuate




The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted Therapy - Download this document for free, or read online. Document in PDF available to download.

Background

This study aimed to elucidate clinical significance of anaplastic lymphoma kinase ALK rearrangement in selected advanced non-small cell lung cancer NSCLC, to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients.

Methods

ALK status was assessed by fluorescent in situ hybridization FISH, immunohistochemistry IHC and quantitative RT-PCR qRT-PCR in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor EGFR mutation.

Results

The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% 59-166, 35.7% 61-171, and 27.9% 34-122, respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival PFS of crizotinib-treated patients was 7.6 months. The overall survival OS of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death P = 0.026. The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival.

Conclusions

Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR.



Author: Ning-Ning Zhang, Yu-Tao Liu, Li Ma, Lin Wang, Xue-Zhi Hao, Zheng Yuan, Dong-Mei Lin, Dan Li, Yu-Jie Zhou, Hua Lin, Xiao-Hong Han,

Source: http://plos.srce.hr/



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