1.Prognostic Significance of p53 Overexpression after Hepatic Resection of Hepatocellular Carcinoma.
Chang Okh SUNG ; Byung Chul YOO ; Kwang Cheol KOH ; Jae Won CHO ; Cheol Keun PARK
The Korean Journal of Gastroenterology 2005;45(6):425-430
BACKGROUND/AIMS: p53 mutation is the most common genetic abnormality in human cancers. However, although it has been reported that p53 overexpression in hepatocellular carcinoma (HCC) is associated with the aggressive behavior of tumor, the prognostic significance of p53 overexpression in HCC remains controversial. The aims of the present study were to examine the correlations between p53 overexpression and the clinicopathologic parameters of HCCs, and to determine the prognostic significance of p53 overexpression in HCC. METHODS: Immunohistochemical analysis of p53 overexpression was performed in 105 consecutive cases of HCC who underwent curative hepatic resection. Survival curves were calculated using the Kaplan-Meier method and multivariate analysis of outcome predictors for HCCs was assessed by logistic regression analysis. RESULTS: p53 overexpression was observed in 20 of 105 HCCs (19.0%). Multivariate analysis identified significant correlations between p53 overexpression and microvascular invasion (p=0.027), liver cirrhosis (p=0.035), 1-year survival rate (p=0.016), multiple tumors (p=0.014), and the presence of tumor capsule (p=0.010). The 2-year survival rate was poorer in patients without tumor capsule (p=0.043). CONCLUSIONS: Our results show a positive association between p53 overexpression and microvascular invasion in HCC, and indicate that p53 overexpression is a poor prognostic factor of survival, especially within 1 year after liver resection in HCC patients.
Adult
;
Aged
;
Carcinoma, Hepatocellular/*metabolism/mortality/surgery
;
Female
;
*Hepatectomy
;
Humans
;
Liver Neoplasms/*metabolism/mortality/surgery
;
Male
;
Middle Aged
;
Prognosis
;
Survival Rate
;
Tumor Suppressor Protein p53/*metabolism
2.Prognostic value of combined expression of Aurora A, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer.
Xue LI ; Ningbo LIU ; Peng REN ; Qinchen CAO ; Peng WANG ; Lujun ZHAO ; Bo LU ; Ping WANG
Chinese Journal of Oncology 2015;37(7):512-516
OBJECTIVEThe aim of this study was to investigate the prognostic value of combined expression of Aurora A, Ki-67, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer (NSCLC).
METHODSExpressions of Aurora A, Ki-67, p53 and p21 WAF1 in 58 tumor samples from resected primary NSCLCs were detected by immunohistochemistry. The correlation of proteins, survival and clinicopathological characteristics was analyzed.
RESULTSThe positive rates of Aurora A, Ki-67, p53 and p21 WAF1 expression were 89.7% (52/58), 53.4% (31/58), 46.6% (27/58) and 34.5% (20/58), respectively. Aurora A expression was positively correlated with nodal metastasis (69.2% vs. 37.8%, P = 0.045). The univariable analysis showed that the overall survival (OS) was 75.0%in patients with low Aurora A expression and 46.0% in patients with high Aurora A expression (P = 0.039). The 3-year survival rate was 40.0% in patients with positive expression of Aurora A and p53, 65.0% in the patients with positive expression of Aurora A or p53, and 82.1% in the patients with negative expression of Aurora A and p53 (P = 0.039). The Cox regression model showed that combined expression of Aurora and p53 is an independent factor affecting the prognosis of NSCLC patients (P = 0.015).
CONCLUSIONSOur findings suggest that the positive expression of Aurora A, Ki-67 and p53 proteins is an unfavorable factor affecting the prognosis for NSCLC patients, and the overexpression of Aurora A is an independent unfavorable factor association with shorter OS in NSCLC patients. Detection of positive Aurora A and p53 expression may be a useful predictive prognostic indicator for NSCLC patients.
Aurora Kinase A ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; surgery ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; surgery ; Prognosis ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism
3.Loss of membranous carcinoembryonic antigen-related cell adhesion molecule 1 expression is related to decreased relapse-free survival of hepatocellular carcinoma following liver transplantation.
Qing-Quan SHA ; Qi-Zhen WEI ; Jian-Kang ZHU ; Ke-Xin WANG ; Chao WANG ; Hai-Tao LIU ; Wen-Bin YU ; Ming-Xia LI ; Guang-Yong ZHANG
Chinese Medical Journal 2012;125(16):2841-2845
BACKGROUNDLoss of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression is an adverse prognostic factor in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival (RFS) following liver transplantation (LT) for HCC.
METHODSExpression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed.
RESULTSOf the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum α-fetoprotein levels (all P < 0.05). Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis (P = 0.027). Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation (P = 0.037).
CONCLUSIONLoss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.
Adult ; Antigens, CD ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; surgery ; Cell Adhesion Molecules ; metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms ; metabolism ; mortality ; surgery ; Liver Transplantation ; Male ; Middle Aged
4.Application of bundles of intervention in the treatment of esophageal carcinoma anastomotic leak.
Wenze TIAN ; Zhongwu HU ; Jian JI ; Dafu XU ; Zhenbing YOU ; Wei GUO ; Keping XU
Chinese Journal of Gastrointestinal Surgery 2016;19(9):1009-1013
OBJECTIVETo investigate the application of bundles of intervention in the treatment of esophageal carcinoma anastomotic leak.
METHODSFrom January 2014 to May 2015, 44 cases of esophageal carcinoma anastomotic fistula were treated by bundles of intervention (through the collection of a series of evidence-based treatment and care measures for the treatment of diseases) in Department of Thoracic Surgery, Huai'an First Hospital, Nanjing Medical University (bundles of intervention group), and 68 patients with esophageal carcinoma postoperative anastomotic leak from December 2013 to January 2012 receiving traditional therapy were selected as the control group. The clinical and nutritional indexes of both groups were compared.
RESULTSThere were no significant differences in general data and proportion of anastomotic leak between the two groups. Eleven patients died during hospital stay, including 3 cases in bundles of intervention group(6.8%) and 8 cases in control group (11.8%) without significant difference(P = 0.390). In bundles of intervention group, 1 case died of type III( intrathoracic anastomotic leak, 2 died of type IIII( intrathoracic anastomotic leak. In control group, 2 cases died of type III( cervical anastomotic leak, 2 died of type III( intrathoracic anastomotic leak and 4 of type IIII( intrathoracic anastomotic leak. The mortality of bundles of intervention group was lower than that of control group. The duration of moderate fever [(4.1±2.4) days vs. (8.3±4.4) days, t=6.171, P=0.001], the time of antibiotic use [(8.2±3.8) days vs.(12.8±5.2) days, t=5.134, P = 0.001], the healing time [(21.5±12.7) days vs.(32.2±15.8) days, t=3.610, P=0.001] were shorter, and the average hospitalization expenses[(63±12) thousand yuan vs. (74±19) thansand yuan, t=3.564, P=0.001] was lower in bundles of intervention group than those in control group. Forty-eight hours after occurrence of anastomotic leak, the levels of hemoglobin, albumin and prealbumin were similar in both groups. However, at the time of fistula healing, the levels of hemoglobin [(110.6±10.5) g/L vs.(103.8±11.1) g/L, t=3.090, P=0.002], albumin [(39.2±5.2) g/L vs.(36.3±5.9) g/L, t=2.543, P=0.013] and prealbumin [(129.3±61.9) g/L vs.(94.1±66.4) g/L, t=2.688, P=0.008] were significantly higher in bundles of intervention group.
CONCLUSIONIn the treatment of postoperative esophageal carcinoma anastomotic leak, application of bundles of intervention concept can significantly improve the nutritional status and improve the clinical outcomes.
Anastomotic Leak ; mortality ; therapy ; Anti-Infective Agents ; therapeutic use ; Carcinoma ; complications ; surgery ; Esophageal Fistula ; complications ; mortality ; therapy ; Esophageal Neoplasms ; complications ; surgery ; Esophagectomy ; adverse effects ; mortality ; Female ; Fever ; epidemiology ; etiology ; Hemoglobins ; metabolism ; Hospital Costs ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Nutritional Status ; Patient Care Bundles ; mortality ; statistics & numerical data ; Prealbumin ; metabolism ; Serum Albumin ; metabolism ; Treatment Outcome
5.Prognostic value of expression of FASE, HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer.
Yan WANG ; Xiang-ru ZHANG ; Jun FU ; Wei TAN ; Wei ZHANG
Chinese Journal of Oncology 2004;26(6):369-372
OBJECTIVETo evaluate the prognostic value of expression of fatty acid synthase (FASE), HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer (NSCLC).
METHODSExpression of FASE, HER-2/neu, bcl-2 and p53 protein was detected by immunohistochemical staining in 84 patients with stage I NSCLC who underwent surgery. Multiple clinical parameters and survival were analyzed.
RESULTSThe expression of FASE, HER-2/neu, bcl-2 and p53 was 29.8%, 40.5%, 33.3% and 39.3%, respectively. The local recurrence and bone-metastasis rate were higher in FASE positive patients than in negative patients (28.0% vs 10.2%, P = 0.05; 61.5% vs 23.9%, P = 0.017, respectively). The 5-year survival rate was lower in HER-2/neu and FASE positive patients than in negative patients (37.7% vs 67.7%, P = 0.0083; 35.1% vs 66.1%, P = 0.0079, respectively), which showed that HER-2/neu and FASE expression were associated with significantly poor survival. Patients whose tumors were both HER-2/neu and FASE negative had better outcome, with a 5-year survival rate of 78.2%, compared with 36.3% in those whose tumors were positive for either one (P = 0.002). However, bcl-2 and p53 were not independent prognostic factors for survival.
CONCLUSIONHER-2/neu and FASE are independent prognostic factor in stage I non-small cell lung cancer patients who expressed one or both markers.
Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; secondary ; surgery ; Fatty Acid Synthases ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; metabolism ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Receptor, ErbB-2 ; metabolism ; Smoking ; adverse effects ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism
6.Expression and clinical impact of vascular endothelial growth factor and matrix metalloproteinase-2 in hepatocellular carcinoma.
Rong-ping GUO ; Chong ZHONG ; Ming SHI ; Chang-qing ZHANG ; Wei WEI ; Ya-qi ZHANG ; Jin-qing LI
Chinese Journal of Oncology 2006;28(4):285-288
OBJECTIVETo investigate the expression and clinical impact of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in hepatocellular carcinoma (HCC).
METHODSNinety specimens obtained from HCC patients were examined immunohistochemically using anti-VEGF and anti-MMP-2 monoclonal antibodies.
RESULTSThe positive rates of VEGF and MMP-2 expression in HCC tissues were 76.7% and 60%, respectively. The expression of MMP-2 in HCC tissues was positively correlated with the expression of VEGF (r(s) = 0.32) and both were positively correlated with recurrence (or metastasis) after hepatectomy (r(s) = 0.31, r(s) = 0.32). 2-year tumor-free survival rates of VEGF- group, VEGF+ group and VEGF++ group were 71.4%, 43.5%, 30.4%, respectively, (P < 0.01), while MMP-2- group 66.7% and MMP-2+ group 32.8% (P < 0.01). Multivariate analysis revealed that the expression of VEGF and MMP-2 in HCC tissues, tumor microthrombus and pre-operative dissemination to lymph nodes were independent recurrence (or metastasis) risk factors.
CONCLUSIONThe expression of VEGF and MMP-2 in HCC tissues, and clinicopathological features (tumor microthrombus and pre-operative dissemination to lymph nodes), could be regarded as valuable indicators for prediction of recurrence (or metastasis) risk in HCC patients.
Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; mortality ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver Cirrhosis ; complications ; Liver Neoplasms ; metabolism ; mortality ; surgery ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; metabolism ; Prognosis ; Proportional Hazards Models ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism
7.Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma.
Seungtaek LIM ; Myoung Ju KOH ; Hyeon Joo JEONG ; Nam Hoon CHO ; Young Deuk CHOI ; Do Yeun CHO ; Hoi Young LEE ; Sun Young RHA
Yonsei Medical Journal 2016;57(4):831-839
PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.
Adult
;
Aged
;
Aged, 80 and over
;
Carcinoma/*metabolism/*mortality/surgery
;
Cystectomy
;
Female
;
Humans
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Muscles/pathology
;
Neoplasm Invasiveness
;
Prognosis
;
Proportional Hazards Models
;
Receptor, ErbB-2/metabolism
;
Receptor, Fibroblast Growth Factor, Type 1/*metabolism
;
Receptor, Fibroblast Growth Factor, Type 3/metabolism
;
Retrospective Studies
;
Survival Rate
;
Urinary Bladder Neoplasms/*metabolism/*mortality/surgery
;
Urothelium/pathology
8.Vascular endothelial growth factor C as a predictor of early recurrence and poor prognosis of resected stage I non-small cell lung cancer.
Shuo Chueh CHEN ; Chuen Ming SHIH ; Guan Chin TSENG ; Wei Erh CHENG ; Jean CHIOU ; Michael HSIAO ; Min Liang KUO ; Jen Liang SU ; Chih Yi CHEN
Annals of the Academy of Medicine, Singapore 2011;40(7):319-324
INTRODUCTIONStage I non-small cell lung cancer (NSCLC) is potentially curable after completely resection, but early recurrence may infl uence prognosis. This study hypothesises that vascular endothelial growth factor C (VEGF-C) plays a key role in predicting early recurrence and poor survival of patients with stage I NSCLC.
MATERIALS AND METHODSThe expression of VEGF-C was immuno-histochemically (IHC) analysed in tumour samples of primary stage I NSCLC and correlated to early recurrence (< 36 months), disease-free survival, and overall survival in all 49 patients.
RESULTSEarly recurrence was identifi ed in 16 patients (33%), and the early recurrence rate in strong and weak VEGF-C activity was significantly different (P = 0.016). VEGF-C was also an independent risk factor in predicting early recurrence (HR = 3.98, P = 0.02). Patients with strong VEGF-C staining also had poor 3-year disease-free survival (P = 0.008) and overall survival (P = 0.007).
CONCLUSIONStrong VEGF-C IHC staining could be a biomarker for predicting early recurrence and poor prognosis of resected stage I NSCLC, if the results of the present study are confirmed in a larger study. A more aggressive adjuvant therapy should be used in this group of patients.
Adult ; Aged ; Aged, 80 and over ; Biomarkers ; blood ; Carcinoma, Non-Small-Cell Lung ; blood ; mortality ; pathology ; surgery ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Taiwan ; Vascular Endothelial Growth Factor A ; blood ; metabolism