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Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.
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<p><b>OBJECTIVE</b>To detect the expression of interleukin-17A(IL-17A) in hepatocellular carcinoma (HCCs) tissues, and to analyze its relationship with clinicopathological characteristics and epithelial-mesenchymal transition (EMT).</p><p><b>METHODS</b>The expression of IL-17A, E-cadherin, vimentin proteins and Snail mRNA were detected by immunohistochemistry and in situ hybridization histochemistry in the hepatocellular carcinoma (HCC) tissues of 74 patients.</p><p><b>RESULTS</b>IL-17A staining was detected in 54.1% (40/74) specimens of human HCCs, but only 25.0% (5/20) in corresponding peritumoral tissues (P<0.05). The positive rate of IL-17A expression in HCC patients with grade III+IV and UICC stage III+IV tumors was significantly higher than those with grade I+II and UICC stage I+II tumors. The expression of IL-17A was positively correlated with portal vein tumor thrombus and microvascular invasion (all P<0.05). The 1- and 2-year recurrence-free survival rates were 27.6% and 17.2% in the patients with positive IL-17A expression, but 79.3% and 58.5% in IL-17A-negative HCCs. The 1- and 2-year overall survival rates were 69.0% and 27.8% in the cases with positive IL-17A expression, while 91.3% and 87.0% in IL-17A-negative cases. Patients with IL-17A-positive HCCs showed significantly shorter recurrence-free and overall survival compared with the patients with IL-17A-negative HCCs (P<0.05). Multivariate analysis indicated that IL-17A expression was an independent factor for recurrence-free and overall survival of HCCs. IL-17A-positive HCCs were characterized by increased expression of vimentin (r=0.492, P<0.01) or Snail (r=0.410, P<0.05) and loss of E-cadherin expression (r=-0.404, P<0.05).</p><p><b>CONCLUSIONS</b>Our results suggest that IL-17A is closely related to epithelial-mesenchymal transition in hepatocellular carcinoma. IL-17A-positive hepatocellular carcinoma demonstrates more aggressive biological behavior, and IL-17A may serve as a potential prognostic marker for this cancer.</p>