• gastroesophageal reflux disease
• mucosal barrier
• mucosal resistance
• reflux esophagitis

The aim of the present study was to investigate the association between tumor protein 53 (TP53) gene deletion and protein expression and clinical features in esophageal squamous cell carcinoma (ESCC), and to evaluate the predictive value of these two characteristics in the prognosis of ESCC. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were performed to detect the expression of p53 protein and gene deletion in ESCC tissue samples from different ethnic groups in Xinjiang, in order to analyze their association with clinicopathological characteristics and patient prognosis, as well as the sensitivity and specificity of the two methods. In addition, the results were further validated by tissue microarray from a different region. The positive rate of p53 protein expression was 54.5% (201/369) in the multi-ethnic group, and was significantly different between sex (P=0.026) and between tumor differentiation groups (P=0.032). FISH demonstrated that the TP53 gene deletion rate was 31.8% (68/214), which was significantly different between different tumor differentiation (P=0.002), lymph node metastasis (P=0.005) and vascular invasion (P<0.001) groups. The survival rate of patients with TP53 gene deletion was significantly lower than those without TP53 gene deletion (P<0.05). The positive rate of p53 protein expression in the tissue microarray was 58.1% (68/117), which was significantly different between the depth of invasion groups (P=0.011). The TP53 gene deletion rate was 47.9% (56/117), which significantly differed according to lymph node metastasis (P=0.003) and TNM stage (P=0.01). In addition, the total concordance rates of the two methods were 60.3 and 64.1%, respectively. There were also significant differences in the positive rate of TP53 gene deletion and protein expression in different stages of ESCC (P<0.05), which increased gradually with the progression of ESCC. The deletion of the TP53 gene in esophageal cancer was associated with poor prognosis and may be an important biomarker for evaluating the prognosis of patients with ESCC. The combination of FISH and IHC methods could significantly improve the detection rate of TP53 gene abnormalities and the accuracy of prognostic assessment of ESCC.

• deletion
• esophageal squamous cell carcinoma
• fluorescence in situ hybridization
• immunohistochemistry
• prognosis
• tumor protein 53

• Apoptosis
• esophageal squamous cell carcinoma
• gene therapy
• lentiviral vector
• miRNA-141
• proliferation.

Immunohistochemistry studies on p53 inactivation in esophageal cancer are available with inconclusive results. Data on the combined effect of p53 protein accumulation and TP53 genomic deactivation in large scale studies for esophageal cancer are currently lacking. A tissue microarray with 691 esophageal cancer samples was analyzed by p53 immunohistochemistry and fluorescence in situ hybridization (FISH). Nuclear p53 accumulation was observed in 45.9% of patients with adenocarcinoma (AC) and in 40.0% in squamous cell carcinoma (SCC). Heterozygous TP53 deletions occurred in 40.9% in AC and in 19.4% in SCC. Homozygous deletions did not occur at all. High-level p53 immunostaining was associated with shortened overall survival in AC and SCC while TP53 deletions alone showed no correlation with survival. High-level p53 immunostaining in patients with AC was associated with advanced tumor (P=0.019) and Union for International Cancer Control stages (P=0.004), grading (P=0.027) and the resection margin status (P=0.006). Associations between p53 immunostaining and SCC were not found. TP53 deletions were found to be associated with advanced tumor stages (P=0.028) and the presence of lymph node metastasis (P=0.009) in SCC. In conclusion, strong p53 immunostaining, but not TP53 deletion alone, is associated with unfavorable outcomes and may therefore represent a clinically useful molecular marker in esophageal cancer.

• esophageal cancer
• outcome
• p53 expression

• Esophageal cancer
• PD-L1
• Receptor tyrosine kinase
• Squamous cell cancer

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/metabolism
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Carcinoma, Squamous Cell/surgery
• Cohort Studies
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Esophagectomy
• Female
• Follow-Up Studies
• Humans
• Immunoenzyme Techniques
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local/metabolism
• Neoplasm Recurrence, Local/pathology
• Neoplasm Recurrence, Local/surgery
• Neoplasm Staging
• Prognosis
• Survival Rate

Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-known biomarkers (p16 and p53) and patient-related factors that may have impact on survival of ESCC.

We conducted a prospective cohort study. By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients’s survival. Survival rates were estimated using Kaplan-Meier methods. A multivariate confirmatory model was performed using Cox proportional hazards regression.

Twelve (13.8%) of 87 patients were HPV-DNA positive. Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan-Meier analysis indicated that men (p = 0.025) had poor specific-cancer survival and a shorter progression-free survival (p = 0.050) as compared to women; III or IV clinical stage (p < 0.019) had poor specific-cancer survival and a shorter progression-free survival (p < 0.001) compared to I and II clinical stage; not submitted to surgery (<0.001) and not submitted to chemoradiotherapy (p = 0.039) had a poor specific-cancer survival, as well. The multivariate analysis showed that HPV, p16 and p53 status are not predictive parameters of progression-free and specific-cancer survival.

HPV infection and p53 and p16 expression are not prognostic factors in ESCC.

• Esophageal cancer
• Human Papillomavirus
• Survival

• Esophageal squamous cell carcinoma
• Immunohistochemical markers
• Prognosis
• Survival

• Biomarkers, Tumor/genetics
• Carcinoma, Squamous Cell/epidemiology
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Esophageal Neoplasms/epidemiology
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma
• Female
• Humans
• Male
• Neoplasm Proteins/genetics
• Prognosis

• CC2016 Arthritis Research UK
• National Natural Science Foundation of China

• Adenocarcinoma/therapy
• Esophageal Neoplasms/therapy
• Esophagus/pathology
• Humans
• Stomach/pathology
• Stomach Neoplasms/therapy

• R01 CA138671 NCI NIH HHS
• R01 CA172741 NCI NIH HHS
• R21 CA127672 NCI NIH HHS

The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer.

Publications that assessed the clinical or prognostic significance of p53 expression in esophageal cancer and were published before July 1, 2015 were identified by searching the PubMed and EMBASE databases. A meta-analysis was performed to clarify the association between p53 expression and the clinical outcomes.

A total of 36 publications met the criteria and included 4577 cases. Analysis of these data showed that p53 expression in esophageal cancer was significantly associated with poorer 5-year survival (RR = 1.30, 95 % CI: 1.11–1.51, P = 0.0008). Subgroup analyses according to histological type, continent of the patients, and cut-off value revealed the similar results. The results also indicated that p53 expression was highly associated with advanced TNM stages (I/II vs. III/IV, OR = 0.74, 95 % CI: 0.55–0.99, P = 0.04), lymph node metastasis (OR = 0.77, 95 % CI: 0.66–0.90, P = 0.001), and distant metastasis (OR = 0.46, 95 % CI: 0.26–0.80, P = 0.006). However, p53 expression in the included studies was not significantly associated with tumor size (≤ 5 cm vs. > 5 cm, OR = 1.13, 95 % CI: 0.92–1.40, P = 0.24), tumor location (upper + middle vs. lower, OR = 0.91, 95 % CI: 0.70–1.17, P = 0.45), grade of differentiation (well + moderate vs. poor, OR = 1.10, 95 % CI: 0.90–1.34, P = 0.35), and the depth of invasion (T1/T2 vs. T3/T4, OR = 0.86, 95 % CI: 0.71–1.03, P = 0.09).

This meta-analysis showed that p53 expression may be a useful biomarker for predicting poorer prognosis in patients with esophageal cancer.

• Esophageal cancer
• Meta-analysis
• Prognosis
• p53

• APOBEC3B
• C > T transition
• Esophageal squamous cell carcinoma
• LINE-1 methylation level
• PIK3CA mutation

Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer and one of the most aggressive types of malignancy, with a high rate of mortality. Early diagnosis and treatment may improve the prognosis of ESCC and, thus, survival rates. As a significant tumor suppressor, p53 is closely associated with apoptosis and the differentiation of cancer cells. The present study evaluated the expression levels of the p53 protein and the clinical significance in patients presenting with ESCC. The p53 protein expression level of 64 paired ESCC and tumor-adjacent normal tissues was evaluated using western blot analysis. In addition, immunohistochemistry (IHC) was performed to detect the p53 expression level in specimens from 118 paraffin-embedded cancerous tissues. The correlation of the p53 expression level with the clinicopathological parameters and prognosis of the ESCC patients was also analyzed. The p53 protein was identified to be highly expressed in the ESCC tissue, with western blot analysis demonstrating that the expression level of p53 in the cancerous tissue was 1.89 times that of the tumor-adjacent normal tissue (P<0.001); furthermore, IHC indicated that there was a marked positive expression of p53 in the ESCC tissue (49.15%). The expression level of p53 protein was identified to be significantly correlated with the tumor grade (P<0.001), N stage (P=0.010). Additionally, the higher level of p53 expression was found to be associated with a poor survival rate in the ESCC patients (P=0.0404). The univariate analysis showed that the survival time of patients was significantly correlated with the T stage (RR=3.886, P<0.001), N stage (lymph node metastasis; RR=3.620, P<0.001) and TNM stage (RR=3.576, P<0.001). Furthermore, the multivariate analysis revealed that the T stage (RR=3.988, P<0.001) and N stage (RR=4.240, P=0.004) significantly influenced the overall survival of the ESCC patients.

• esophageal squamous cell carcinoma
• immunohistochemistry
• p53
• prognosis
• western blot

Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstays of current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.

• Esophageal cancer
• Esophageal cancer staging
• Esophageal squamous cell carcinoma
• Esophageal adenocarcinoma
• Surgery

AIM: To investigate adjuvant chemotherapy, p53 and carcinoembryonic antigen (CEA) expression and prognosis after D2 gastrectomy for stage II/III gastric adenocarcinoma.

METHODS: A total of 286 patients with stage II or III gastric adenocarcinoma who underwent D2 radical gastrectomy between May 2007 and December 2010 were enrolled into this study. One hundred and sixty-nine of these patients received surgery plus adjuvant chemotherapy, and 117 patients received surgery alone. Tumor expression of p53 and CEA proteins in all patients was evaluated immunohistochemically and correlated with clinicopathological parameters. The Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) with log-rank testing were used to compare the survival difference. A Cox proportional hazard regression model was used for multivariate analysis.

RESULTS: Patients with adjuvant chemotherapy had a significantly better median OS (50.87 mo vs 30.73 mo, P = 0.000) and median DFS (36.30 mo vs 25.60 mo, P = 0.001) than patients with surgery alone in the entire cohort. Consistent results with the entire cohort were found in stage II (P = 0.006 and P = 0.047), stage III (P = 0.005 and P = 0.030), and stage IIIB/IIIC patients (P = 0.000 and P = 0.001). The median OS and DFS advantages were confirmed by multivariate analysis (P = 0.000 and P = 0.008) and maintained when the analyses were restricted to fluoropyrimidine monotherapy (P = 0.003 and P = 0.001) and fluoropyrimidine plus platinum regimen (P = 0.001 and P = 0.007), however, not the fluoropyrimidine plus taxane (P = 0.198 and P = 0.777) or platinum plus taxane (P = 0.666 and P = 0.687) regimens. Median OS and median DFS did not differ significantly between the patients with p53(+) and p53(-) tumors (P = 0.608 and P = 0.064), or between patients with CEA(+) and CEA(-) tumors (P = 0.052 and P = 0.989), which were maintained when the analyses were restricted to surgery alone (p53: P = 0.864 and P = 0.431; CEA: P = 0.142 and P = 0.948), adjuvant chemotherapy (p53: P = 0.802 and P = 0.091; CEA: P = 0.223 and P = 0.946) and even different chemotherapy regimens (P > 0.05).

CONCLUSION: Patients after D2 gastrectomy for stage II/III gastric adenocarcinoma had significantly better survival after fluoropyrimidine monotherapy and fluoropyrimidine plus platinum. p53 and CEA were not prognostic.

• Gastric adenocarcinoma
• Adjuvant chemotherapy
• p53
• Carcinoembryonic antigen
• Immunohistochemistry

• Adenocarcinoma/immunology
• Adenocarcinoma/mortality
• Adenocarcinoma/secondary
• Adenocarcinoma/surgery
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carcinoembryonic Antigen/analysis
• Chemotherapy, Adjuvant
• Chi-Square Distribution
• Disease Progression
• Disease-Free Survival
• Female
• Gastrectomy/adverse effects
• Gastrectomy/methods
• Gastrectomy/mortality
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Recurrence, Local/prevention & control
• Neoplasm Staging
• Patient Selection
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Stomach Neoplasms/immunology
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Time Factors
• Treatment Outcome
• Tumor Suppressor Protein p53/analysis