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Secondary KIT gene amplification leads to tyrosine kinase inhibitor resistance in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC). The presence of the 4q12 amplicon causes the activation of downstream mast/stem cell growth factor receptor Kit (c-Kit) or platelet-derived growth factor receptor α (PDGFRA) signaling pathways. Therefore, in the present study, the association between the functional proteins phosphorylated c-Kit (p-c-Kit) and phosphorylated PDGFRA (p-PDGFRA) and the prognosis of ALK fusion NSCLC was investigated. Advanced stage NSCLC samples with ALK fusion were tested for their p-c-Kit and p-PDGFRA content by immunohistochemical staining, and for its association with crizotinib efficacy and the survival of the patients. Of 64 eligible ALK-positive patients with NSCLC, 30 (46.9%) were p-c-Kit-positive and 10 (15.7%) were p-PDGFRA-positive. Brain metastases were more common in ALK-positive cases that were p-PDGFRA-positive compared with those who were p-PDGFRA-negative. ALK-positive patients treated with crizotinib, who exhibited high levels of p-c-Kit had significantly lower progression-free survival times than those with low levels. In addition, the patients with high levels of p-c-Kit exhibited lower overall survival times than those with low levels. Furthermore, multivariate analysis indicated that high levels of p-c-Kit in patients with ALK fusion was the only significant predictive factor for crizotinib efficacy and was a prognostic factor for poor overall survival time. However, no statistically significant difference was observed in the survival of patients with different p-PDGFRA levels. p-PDGFRA was more frequently expressed in the ALK-positive cases with brain metastasis. c-Kit signaling activation may be associated with poor efficacy of crizotinib and poor prognosis in advanced ALK fusion NSCLC. [ABSTRACT FROM AUTHOR]

Background: CD44 is a marker for colorectal cancer (CRC) stem cells (CCSCs), but its prognostic value remains controversial. Furthermore, few studies have investigated the expression profile of CD44 variants in CRC. The proto-oncogene mast/stem cell growth factor receptor Kit (c-Kit) was previously found to play an important role in supporting CRC cells; however, the associations between c-Kit and CD44 (and its splice variants) remain largely unknown., Methods: A total of 148 patients with CRC were enrolled in the present study, and the levels of CD44, CD44 splice variant (v)3, CD44v6 and c-Kit were examined by immunohistochemical staining. Associations between these markers and clinicopathological parameters, as well as the extent to which these markers predict progression free-survival (PFS), were analyzed., Results: A total of 29 (19.6%), 60 (40.5%) and 66 (44.6%) patients were CD44-, CD44v3- and CD44v6-positive, respectively. No clear c-Kit-positivity was detected in any of the patients. Analyses of clinicopathological features indicated that positive expression of CD44v3 was significantly associated with cell differentiation (P=0.03), and N (P=0.04), M (P<0.01) and tumor-node-metastasis (TNM) stages (P<0.01). Univariate analysis demonstrated that T, N, M and TNM stages (all P<0.01), and CD44 (P<0.01), CD44v3 (P=0.03) and CD44v6 (P=0.02) levels were significantly associated with PFS. Furthermore, multivariate analysis indicated that patients without CD44 expression (P<0.01) but with CD44v3 (P=0.04) and CD44v6 (P=0.02) expression exhibited significantly shortened PFS., Conclusions: CD44, CD44v3 and CD44v6 were determined to be heterogeneously expressed in CRC, and may aid in the prognostic prediction of patients with this disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2020.02.12). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)