Analysis Of Clinicopathological Features And Prognosis Of Patients From Core Families Of Esophageal Cancer

1 Background and objectiveEsophageal cancer is one of the six most common malignant tumors in the world.It ranks seventh in incidence and sixth in mortality.China is one of the countries with the highest incidence and mortality of esophageal cancer in the world.There are about 570,000 new cases of esophageal cancer in the world every year,nearly half of which occur in China.The prognosis of esophageal cancer is very poor.The 5-year survival rate of advanced patients is only about 15%,while that of early patients can be as high as 90%.However,because the symptoms of early esophageal cancer are not obvious and there is no effective detection method in clinic,the detection rate of early esophageal cancer is very low,only about 5%.Therefore,it is essential to elucidate the molecular mechanism of high susceptibility to esophageal cancer,screen susceptible genes,establish molecular typing and early detection molecular marker screening system for high risk population,so as to improve the detection rate of early esophageal cancer,prolong the survival time of patients and reduce mortality.Family aggregation is one of the prominent epidemiological features of esophageal cancer,which is characterized by multiple members of a family suffering from esophageal cancer.In the 1970 s,an epidemiological survey of esophageal cancer found that 32 people in a family suffered from esophageal cancer for five consecutive generations.It was also common for families with esophageal cancer(> 3 cases)in three consecutive generations.Family aggregation of esophageal cancer suggests that genetic factors may play an important role in the occurrence of esophageal cancer.Core family of esophageal cancer(2 or more cases of esophageal cancer occurring in two successive generations)is a typical manifestation of family aggregation of esophageal cancer with characteristics of high susceptibility and high incidence.Families with complete data and sample information are the best models for screening and locating esophageal cancer susceptibility and driving candidate genes,and are the excellent samples for elucidating the molecular mechanism of esophageal cancer.The P53 is a common tumor suppressor gene.Wild type P53 can inhibit tumors by regulating cell growth,proliferation and inducing apoptosis.Many studies have shown that more than half of patients with malignant tumors have mutations in P53.The expression of P53 is closely related to the recurrence rate and 5-year survival rate of esophageal cancer.However,few studies has reported the effect of P53 expression on the prognosis of patients with esophageal cancer in core families.During the past 45 years(1973-2018),we have established a database of clinical diagnosis,treatment,follow-up information for 500,000 cases of esophageal/gastric cardia cancer.In this process,through prospective follow-up studies,a large number of core families of esophageal cancer have been accumulated,and the clinical diagnosis,treatment,follow-up and sample information of the probands and their offspring of esophageal cancer patients are complete.Therefore,on the basis of previous work,this study preliminarily explored the clinicopathological features and prognosis of patients from core family of esophageal cancer,and further analyzed the expression of P53 in patients and its clinical significance,so as to provide theoretical support and molecular basis for early warning,early detection and prognosis judgement for high risk population of esophageal cancer.2 Materials and methods 2.1 Object of studyA total of 3,260 patients with esophageal squamous cell carcinoma were enrolled in this study.All information came from the database of 500,000 cases of esophageal/gastric cardia cancer in Henan Key Open Laboratory of Esophageal Carcinoma,the First Affiliated Hospital of Zhengzhou University.3,260 patients came from 3,260 core families of esophageal cancer.All patients had complete clinicopathological information and underwent radical esophagectomy of esophageal cancer.2.2 Methods(1)Through retrospective analysis of the clinical diagnosis and treatment data of 3260 patients with esophageal cancer in core families,explore the clinical and pathological features,including gender,diagnosis age,high and low incidence area,tumor location,long diameter,differentiation degree,margin,TNM staging,etc,of esophageal cancer patients from core families,and the relationship between these clinical features and the prognosis of patients.(2)150 patients were randomly selected for immunohistochemical staining to detect the expression of P53,and to analyze the relationship between P53 expression and clinicopathological features and prognosis of patients from core families of esophageal cancer.(3)SPSS25.0 software was used for statistical analysis.The survival time was calculated in terms of years.Kaplan-Meier method and log-rank test were used for univariate analysis.Cox proportional risk model was used for multivariate analysis.The test level was 0.05.3 Results 3.1 Clinicopathological characteristics of esophageal cancer patients in core familiesAmong the 3,260 patients with esophageal cancer in core families,2,043 were males,with a male to female ratio of 1.7:1;53.8%(1,755/3,260)were diagnosed with age over 60 years old,the youngest age was 32 years old,the oldest age was 85 years old,and the average age of diagnosis was 60.2 ± 8.1 years;88.8%(2,896)patients came from the high incidence area of esophageal cancer,the ratio of high incidence area to low was 8.0:1;cervical + upper segment: 486 cases,middle + lower segment: 2,774 cases;There were 376 cases(11.5%),2,017 cases(61.9%)and 867 cases(26.6%)of highly,moderately and poorly differentiated esophageal cancer;1,552 cases(47.6%)with a diameter less than 4cm,708 cases(52.4%)with a diameter greater than 4cm;3,075 cases(94.3%)with a clear margin,185 cases(5.7%)with atypical hyperplasia or cancer after operation;TNM stage: 0+Ⅰ,Ⅱ,Ⅲ,Ⅳ were 494 cases(15.2%),1,776 cases(54.5%),976 cases(29.9%)and 14 cases(0.4%),respectively.3.2 Prevalence of esophageal cancer in core families3,260 patients with esophageal cancer were from 3,260 core families of esophageal cancer.The number of families with esophageal cancer 2,3,4 and ≥5 in two consecutive generations were 2,527(77.5%),583(17.9%),116(3.6%),34(1.0%),respectively.There are up to 8 patients with esophageal cancer in a single core family.There were 2,527 core families with 2 cases of esophageal cancer,687(27.2%)of father-child type,548(21.7%)of mother-child type,353(14.0%)of father-daughter type,and 365(14.4%)of mother-daughter type and 574(22.70%)of siblings type.3.3 Analysis of prognostic factorsUnivariate analysis showed that gender,age of diagnosis,location of tumor,degree of differentiation,length of tumor and TNM stage were associated with the prognosis of esophageal cancer patients in core families(P<0.05).Multivariate analysis showed that males,diagnosed age ≥60 years,cervical + upper segment,low degree of differentiation,tumor long diameter ≥4 cm and late TNM were independent risk factors for the prognosis of esophageal cancer patients in core families(P < 0.05).3.4 The expression of P53 in esophageal cancer patients of core familyThe positive rate of P53 expression was 56.0%(84/150)in esophageal cancer patients of core families,including 9 mosaic,8 focal and 67 diffuse types.3.5 The relationship between P53 expression and clinicopathological characteristics of esophageal cancer in core familiesThe positive rate of P53 expression in esophageal cancer patients of core families had no statistical difference in sex,age,high and low incidence area,tumor location,differentiation degree,tumor margin and length,T,N,M and TNM stages(all P > 0.05).3.6 The influence of P53 expression on the prognosis of esophageal cancer patients in core familiesThere was significant difference in survival rate between the positive and negative groups of P53 expression in esophageal cancer patients of core families(χ2=10.114,P= 0.001).4 Conclusions(1)Among the patients with esophageal cancer in the core families,males were more than females.The patients with diagnostic age ≥ 60 years old,high incidence area,middle and Lower segments,moderate differentiation,tumor length ≥ 4cm and net resection margin were more common.The patients with TNM stage II were the most,while those with stage IV were the least.(2)Among the core families of esophageal cancer,2 cases of esophageal cancer and father-child type were the most common.(3)Sex,age of diagnosis,location of tumors,degree of differentiation,tumor length and TNM stage are independent prognostic factors of esophageal cancer patients in core families.(4)The positive rate of P53 expression in esophageal cancer patients of core families is not related to different clinicopathological characteristics.P53 expression may be a frequent molecular event in the occurrence and development of esophageal cancer.(5)The survival rate of P53 negative expression in patients with esophageal cancer in core families is better than that in positive families.The expression of P53 can be used as a reference index to judge the prognosis of patients with esophageal cancer in core families..