Yu Guo1, Lin Zhang2,3,4, Ning Zhang1, Luohai Chen1, Qiuyun Luo2,3,5, Man Liu1, Dajun Yang6,7, Jie Chen8,9,10,11. 1. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. 2. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. 3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. 4. Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. 5. The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China. 6. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. yangdj@sysucc.org.cn. 7. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. yangdj@sysucc.org.cn. 8. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. chen0jie@hotmail.com. 9. Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. chen0jie@hotmail.com. 10. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. chen0jie@hotmail.com. 11. Department of Head & Neck tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center Shanghai, Shanghai, 200032, China. chen0jie@hotmail.com.
Abstract
PURPOSE: Bcl-2 family proteins are of great significance in the pathogenesis and development of tumors. In this study, the correlations between the expression of Bcl-2 family proteins and clinicopathological features and prognosis of neuroendocrine neoplasms (NENs) were further investigated. METHODS: 105 Patients diagnosed with gastroenteropancreatic NENs (GEP-NENs) with the paraffin specimen of the tumor available were retrospectively included. Immunohistochemistry (IHC) was performed to detect the expression of Bcl-2 family proteins in paraffin-embedded samples. Student's t-test and Chi-square test were applied to compare the difference of quantitative and categorical variables, respectively. Survival analysis was conducted according to Kaplan-Meier method. Univariate and multivariate cox regression analysis were used to identify the independent prognostic factors. RESULTS: The IHC score of Bcl-2 was significantly higher in neuroendocrine carcinoma (NEC) patients (65.6%), while a higher IHC score of Noxa was more common in neuroendocrine tumor (NET) patients (49.3%). Survival analysis indicated that patients with higher Bcl-2 expression and lower Noxa expression had worse 5-year survival (39.3% vs. 75.6%, p < 0.001; 40.6% vs. 84.9%, p < 0.001). Multivariate cox analysis indicated that high Bcl-2 expression was an independent factor associated with inferior DFS (hazard ratio [HR]: 2.092; 95% confidence interval [CI]: 1.106-3.955; p = 0.023) and OS (HR: 2.784; 95% CI: 1.326-5.846; p = 0.007), while higher Noxa expression was associated with superior DFS (HR:0.398; 95% CI: 0.175-0.907; p = 0.028) and OS (HR: 0.274; 95% CI: 0.110-0.686; p = 0.006). CONCLUSIONS: Higher expression of Bcl-2 and lower expression of Noxa were associated with unfavorable prognosis of GEP-NENs patients.
PURPOSE: Bcl-2 family proteins are of great significance in the pathogenesis and development of tumors. In this study, the correlations between the expression of Bcl-2 family proteins and clinicopathological features and prognosis of neuroendocrine neoplasms (NENs) were further investigated. METHODS: 105 Patients diagnosed with gastroenteropancreatic NENs (GEP-NENs) with the paraffin specimen of the tumor available were retrospectively included. Immunohistochemistry (IHC) was performed to detect the expression of Bcl-2 family proteins in paraffin-embedded samples. Student's t-test and Chi-square test were applied to compare the difference of quantitative and categorical variables, respectively. Survival analysis was conducted according to Kaplan-Meier method. Univariate and multivariate cox regression analysis were used to identify the independent prognostic factors. RESULTS: The IHC score of Bcl-2 was significantly higher in neuroendocrine carcinoma (NEC) patients (65.6%), while a higher IHC score of Noxa was more common in neuroendocrine tumor (NET) patients (49.3%). Survival analysis indicated that patients with higher Bcl-2 expression and lower Noxa expression had worse 5-year survival (39.3% vs. 75.6%, p < 0.001; 40.6% vs. 84.9%, p < 0.001). Multivariate cox analysis indicated that high Bcl-2 expression was an independent factor associated with inferior DFS (hazard ratio [HR]: 2.092; 95% confidence interval [CI]: 1.106-3.955; p = 0.023) and OS (HR: 2.784; 95% CI: 1.326-5.846; p = 0.007), while higher Noxa expression was associated with superior DFS (HR:0.398; 95% CI: 0.175-0.907; p = 0.028) and OS (HR: 0.274; 95% CI: 0.110-0.686; p = 0.006). CONCLUSIONS: Higher expression of Bcl-2 and lower expression of Noxa were associated with unfavorable prognosis of GEP-NENs patients.
Authors: T C Fisher; A E Milner; C D Gregory; A L Jackman; G W Aherne; J A Hartley; C Dive; J A Hickman Journal: Cancer Res Date: 1993-07-15 Impact factor: 12.701