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Prognostic implications of FGFR1 and MYC status in esophageal squamous cell carcinoma

World Journal of Gastroenterology 2016年第44期22卷 9803-9812页

作者： Dohee Kwon Ji Yun Yun bhumsuk keam Young Tae Kim Yoon Kyung Jeon Department of Pathology Seoul National University Hospital Seoul National University College of Medicine Department of Internal Medicine Seoul National University Hospital Seoul National University College of Medicine Department of Thoracic Surgery Seoul National University Hospital Cancer Research Institute Genomic Medicine Institute Seoul National University College of Medicine Seoul National University College of Medicine

AIM To investigate the clinicopathological features and prognostic implications of combined MYC and fibroblast growth factor receptor 1(FGFR1) status in esophageal squamous cell carcinomas(ESCCs). METHODS All patients with ESCC(n = 180) underwent surgical resection at Seoul National University Hospital sometime between 2000 and 2013. A tissue microarray was constructed using cores obtained from representative tumor areas of formalin-fixed, paraffin-embedded tissue blocks. FGFR1 and MYC copy numbers were quantified using fluorescence in situ hybridization. The level of MYC expression was determined using immunohistochemistry. FGFR1 and MYC amplification status was compared between primary and metastatic lymph nodes. Univariate and multivariate survival analyses were performed according to adjuvant therapy *** FGFR1 and MYC amplifications were observed in 21.4%(37/173) and 54.2%(91/168) of patients, respectively, while MYC expression was observed in 58.9%(106/180) of patients. There was a positive correlation between MYC amplification and overexpression(P = 0.002). Although FGFR1 amplification was not associated with MYC amplification or expression, 12.3%(20/163) of patients exhibited both FGFR1 amplification and MYC expression. There was also a correlation in FGFR1 amplification status between matched primary tumors and metastatic lymph nodes(P < 0.001). MYC expression was higher in ESCCs with p T1(P < 0.001) and in those with no lymph node metastasis(P = 0.023). MYC expression was associated with prolonged diseasefree survival(P = 0.036) and overall survival(OS)(P = 0.017) but was not an independent prognostic factor. FGFR1 amplification was an independent predictor for prolonged OS in all patients(P = 0.029) and in those who did not receive adjuvant therapy(P = 0.013). Combined FGFR1 amplification and MYC expression predicted better OS in patients who did not receive adjuvant therapy(P = 0.034) but not in those who did receive adjuvant ***

关键词： Receptor tyrosine kinase Fibroblast growth factor receptor 1 MYC Esophageal squamous cell carcinoma Gene amplification Prognosis Fluorescent in situ hybridization

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Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2016年第37期22卷 8389-8397页

作者： Ryul Kim bhumsuk keam Dohee Kwon Chan-Young Ock Miso Kim Tae Min Kim Hak Jae Kim Yoon Kyung Jeon In Kyu Park Chang Hyun Kang Dong-Wan Kim Young Tae Kim Dae Seog Heo Department of Internal Medicine Seoul National University HospitalSeoul 03080South Korea Cancer Research Institute Seoul National University College of MedicineSeoul 03080South Korea Department of Pathology Seoul National University HospitalSeoul 03080South Korea Department of Radiation Oncology Seoul National University HospitalSeoul 03080South Korea Department of Thoracic and Cardiovascular Surgery Seoul National University HospitalSeoul 03080South Korea

AIM To investigate the expression and prognostic role of programmed death ligand-1(PD-L1) in locally advanced esophageal squamous cell carcinoma(ESCC).METHODS A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed. RESULTS Tumor tissues from 67 ESCC patients(33.5%) were PDL1-positive. Positive p16 expression was observed in 21 specimens(10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens(21.0%). Although PDL1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PDL1-positivity(OR = 2.34, 95%CI: 1.16-4.72, P = 0.017). PD-L1 expression was not significantly associated with a change in overall survival(P = 0.656). In contrast, the locoregional relapse rate tended to increase(P = 0.134), and the distant metastasis rate was significantly increased(HR = 1.72, 95%CI: 1.01-2.79, P = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative *** PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC.

关键词： Esophageal neoplasm Programmed death ligand-1 protein c-Met protein Prognosis p16INK4A protein

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