| 1 Background and AimEsophageal cancer is one of the most common malignant tumors in the world,China is one of the countries with the highest incidence and mortality rate of esophageal cancer in the world.In recent years,the incidence and mortality of esophageal cancer in China has been high.According to reports,the incidence of esophageal cancer is 21.17/10 million,and ranks fifth in all kinds of malignant tumors;The mortality rate was 15.58/10 million,and ranks fourth in cancer-related fatal tumors.At present,radical surgery is still the first choice for the treatment of esophageal cancer.However,the 5 year survival rate was less than 30%.Although the examination to esophageal cancer has improved in recent years,people’s awareness of cancer prevention is also improved,but the efficacy of esophageal cancer has not been improved.The main reason is that the majority of patients with esophageal cancer early clinical symptoms are not typical,when clinical symptoms appear again,patients has been in advanced stages,and there are only a few people who are able to undergo surgery for esophageal cancer.However,the patients who undergo radical resection of esophageal cancer,there are will soon have tumor recurrence,lymph node metastasis or distant metastasis after surgery.So,at present,it is difficult to further improve the 5 year survival rate of patients with surgery alone.Studies have shown that preoperative radiotherapy can deflate the tumor,eliminate micrometastasis of tumor,so as to improve the survival rate of patients with surgery.Besides,some patients in late stage can regain the chance of curative surgery by the treatment.However,in recent years,the clinical reports about the preoperative radiotherapy can improve the survival on patients with esophageal cancer are not consistent.This inconsistency may be related to the difference in radiosensitivity.So,radiosensitivity measurement before preoperative radiotherapy would be valuable for individualized treatment.Previous studies have demonstrated that p53 gene is one of the most closely related genes in radiosensitivity.The normal function of p53 gene plays a key role in promoting apoptosis and enhancing tumor cell radiosensitivity.In this study,a total of 645 cases of esophageal squamous cell carcinoma were divided into 2 groups: preoperative radiotherapy group and surgery alone group,to investigate the impact of preoperative radiotherapy on the survival of advanced esophageal squamous cell carcinoma patients.And combine with the expression of p53 in samples before and after radiotherapy with immunohistochemistry method,to evaluate the relationship between the expression of p53 and efficacy and prognosis of preoperative radiotherapy in squamous esophageal carcinoma,to provide an important basis for accurate treatment of esophageal cancer.2 Materials and Methods 2.1 Objects 2.1.1 Impact of preoperative radiotherapy on the survival of advanced esophageal squamous cell carcinoma patientsA total of 645 esophageal squamous cell carcinoma patients with advanced stage were enrolled in this study.All the clinical information was derived from the databases of 500,000 esophageal and gastric cardiac carcinomas(1973-2015)of the Henan Key Laboratory for Esophageal Cancer Research.These patients were divide into 2 groups: preoperative radiotherapy group with a total of 226 cases(140 males with an average diagnosed age of 58.83±8.67 years and 86 females with an average diagnosed age of 60.46±9.24 years)and surgery alone group with a total of 419 cases(250 males with an average diagnosed age of 59.23±7.94 years and 169 females with an average diagnosed age of 60.29±9.02 years).2.1.2 The expression of p53 as prediction to curative effect and prognosis of preoperative radiotherapy in esophageal squamous cell carcinomaA total of 86 esophageal squamous cell carcinoma patients who accepted preoperative radiotherapy were selected in laboratory database.56 males with an average diagnosed age of 61.05±8.45 years and 30 females with an average diagnosed age of 60.33±9.46 years.And 30 cases of normal esophageal mucous membrane wax were selected as control group,there were 18 males and 12 females,with an average diagnosed age of 58.86±8.83 years.2.2 Collection and collation of data subjectsThe basic information of the study is mainly from the large-scale epidemiological investigation,and combines with the patient’s hospital to find the clinical information.Then the clinical data of the patients were arranged,and input data in the Microsoft Office Excel 2007.2.3 RadiotherapyThe conventional external irradiation with 6MV Linear Accelerator was applied to the preoperative radiotherapy group with a total of 40-60Gy/4-6weeks.The surgical treatment was followed after 2-4 weeks radiotherapy.Three dimensional conformal radiotherapy was used after patients received CT simulation,the target delineation was accomplished by a number of experienced radiologists.2.4 SurgeryAll patients underwent radical resection through left-side thoracotomy under general anesthesia,by left cervical esophagogastrostomy,by supra aortic arch esophagogastrostomy,and the other by inferior aortic arch esophagogastrostomy.2.5 ImmunohistochemistryThe expression of p53 in samples before and after radiotherapy were detected with SABC inmunohistochemistry method,and 30 cases of normal esophageal mucous wax were selected as control group.2.6 Follow-up of survivalAll patients were followed up regularly by telephone and household surveys.Every three months to half a year for a follow-up,and the death is the final event.The end of follow-up time was September 30,2015,a total of 612 patients were followed up successfully,the follow-up rate was up to 95%,All of the 86 patients with esophageal squamous cell carcinoma who were selected for immunohistochemistry were followed up successfully,the follow-up rate was up to 100%.2.7 Statistical analysisThe SPSS21.0 statistical software was applied for all the data analysis.Chi square test was used to analyze the clinical characteristics of the two groups;The survival rate was calculated based on Kaplan-Meier and Log-rank analysis mode;.Multivariate analysis of prognostic factors of esophageal cancer by COX proportional hazards regression.At the test level P < 0.05,the difference was statistically significant.3 Results 3.1 Survival analysis of two groups with different age and genderIn male patients,the median overall survival of preoperative radiotherapy group were 5.29 years and surgery alone group were 5.52 years,P=0.158;In female patients,the median overall survival of two groups were 8.87 years and 6.00 years,P=0.426.The median overall survival of patients under 50 years of age in two groups were 5.64 years and 6.90 years,P=0.92,the median overall survival of patients over 50 years of age in two groups were 6.10 years and 5.43 years,P=0.775.3.2 Survival analysis of two groups with different pathological featuresThe median overall survival of upper thoracic ESCC in preoperative radiotherapy group were 5.49 and surgery alone group was years 7.15 years,P=0.221;The median overall survival of middle thoracic ESCC in two groups were 7.21 years and 5.16 years,P=0.471;The median overall survival of lower thoracic ESCC in two groups were 6.38 years and 7.24 years,P=0.134.The median overall survival of esophageal cancer patients with stage II in two groups were 5.74 years and 6.90 years,P=0.458;The median overall survival of esophageal cancer patients with stage III in two groups were 4.73 years and 3.96 years,P=0.997.The median overall survival of lymph node positive in two groups were 5.67 years and 4.68 years,P=0.908;The median overall survival of lymph node negative in two groups were 5.62 years and 7.15 years,P=0.172.3.3 Overall survival analysis of the two groupsThe above factors into the overall analysis shows,the median overall survival of preoperative radiotherapy group were 5.64 years(95%CI: 4.55~6.79 years),the 1-,3-and 5-year overall survival rates were 76%,57% and 49%;The median overall survival of surgery alone group were 5.67 years(95%CI: 3.92~7.35 years),the 1-,3-and 5-year overall survival rates were 81%,62% and 49%,There was no significant difference for the two groups(P=0.577).3.4 The relationship between clinicopathologic features and prognosisSingle factor analysis showed,gender,age,degree of differentiation,depth of invasion,lymph node metastasis,lymphovascular invasion had significant relationship with the prognosis of advanced esophageal squamous cell carcinoma(P<0.05).Multivariate COX regression model analysis showed that age,degree of differentiation,depth of invasion,lymph node metastasis,lymphovascular invasion were independent prognostic factors(P<0.05).3.5 The expression of p53 as prediction to curative effect and prognosis of preoperative radiotherapy in esophageal squamous cell carcinomaThe positive rate of p53 expression in esophageal squamous cell carcinoma was significantly higher than that in normal esophageal mucosa(p=0.000);The positive expression of p53 was correlated with the degree of differentiation and lymph node metastasis(p<0.05),but the positive expression of p53 was not related to gender,age and,deepth of invasion(p>0.05).The expression of p53 was different in the short-term efficacy of radiotherapy,the p53 negative expression group was significantly better than the p53 positive expression group(P=0.034).The positive expression rate of p53 in esophageal carcinoma before radiotherapy was lower than that after radiotherapy,but the difference was not statistically significant(P > 0.05);The median overall survival of p53 negative expression group was 4.29 years(95CI:3.66~7.58 year),the median overall survival of p53 positive expression group was 2.05 years(95CI:1.88~6.38 years),respectively,there was significant difference for the two groups(p=0.037).4.conclusions1)The present study demonstrates that,comparing with surgery alone,the preoperative radiotherapy does not show any improvement on the survival of advanced esophageal squamous cell carcinoma patients.2)Age,degree of differentiation,depth of invasion,lymph node metastasis,and lymphovascular invasion were the independent prognostic factors for the overall survival of the patients.3)The expression of p53 can be used as sensitive indicator to evaluate the curative effect and prognosis of preoperative radiotherapy in esophageal squamous cell carcinoma. |
