Clinicopathological Characteristics,Survivals Factors And TP53 Mutation Analysis Of Primary Malignant Melanoma Of Esophagus

1 Backgrounds and ObjectivesMelanoma,which is one of the most widespread malignant tumors in the world,cutaneous melanoma is the most common type of melanoma,accounting for more than 90%.Other ways to say,visceral melanoma is very rare and gastrointestinal tumors are extremely rare.Esophageal melanoma's proportion is about 0.5%of all malignant melanomas and it account for 0.1%to 0.2%of all esophageal tumors.TP53 has hot mutations in human tumors,is the most prone to mutation of the anti-cancer gene,wild type P53 can regulate cell growth and reproduction,induce cell apoptosis,thereby inhibiting the occurrence of tumor.Studies have shown that TP53 mutates more than 90%in esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinomas,and TP53 mutations are associated with the survival of esophageal cancer.Primary malignant melanoma of esophagus(PMME)is a special histology type of esophageal cancer,which has similar clinical manifestations with esophageal cancer,and the mutation of TP53 mutation in PMME and its effect on survival is rarely reported.Whether its characteristics are similar to ESCC needs further study.The purpose of this study is to investigate the clinicopathological characteristics of PMME patients,analyze the prognostic factors of PMME patients,and further observe the mutation of TP53 in PMME and its relationship with survival.2 Patients and Methods2.1 PatientsThis study included a total of 210 PMME patients,the clinical,pathological and survival follow-up information of all patients were from the 500,000 cases of esophageal cancer and gastric cardia adnocarcinoma information and biological samples of the State key laboratory of esophageal cancer prevention and treatment.Of these,159 were male,with an average diagnostic age of 58.4 to 9.0 years,and 51 females with an average diagnostic age of 55.5 to 11.3 years.2.2 Methods? The clinical information of 210 PMME patients was analyzed retrospectively,including gender,age of diagnosis,smoking,drinking,family history,pathological information(including pathological diagnosis,tumor location,tumor length,general type,invasion degree,lymph node metastasis,TNM stage,margin),Immunohistochemistry,diagnosis time and survival follow-up.To analyze the clinicopathological characteristics and its influence on the survival of patients.? 15 patients with PMME and 33 patients with ESCC were selected for targeted sequencing,of which the tissue samples and clinical information is complete.The original sequencing data were compared and analyzed to screen out meaningful mutations and record mutation types.? IBM SPSS 25.0 was used for analysis,Kaplan-Meier method(log rank test)and Cox regression model were used to analyze the prognostic factors,and chi square test and Fisher exact probability method were used to analyze whether TP53 mutation was different in PMME and ESCC.The test level was 0.05.3 Results3.1 Clinicopathological characteristics of PMMEAmong 210 PMME patients,159(75.7%)were male,51(24.3%)were female,the ratio of male to female was 3.1:1;the main complaints of the first visit were choking(176,83.8%),5 were swallowing pain(2.4%),11 were abdominal discomfort(5.2%)and 16 were sternal discomfort(7.6%),1 was neck tumor(0.5%),1 was physical examination(0.5%);12 were family history positive(21.4%),44 were negative(78.6%);the tumor site was mainly in the lower thoracic segment(120 cases,57.1%),followed by the middle thoracic segment(81 cases,38.6%),less in the neck and upper thoracic segments(9 cases 4.3%);the polyp type was the most(55 cases,36.4%),the medulla type was the least(8 cases,5.3%),the ulcer type,uplift type,cavity type and mushroom umbrella type were 16 cases(10.6%),32 cases(21.2%),13 cases(8.6%)and 27 cases(17.9%)respectively.3.2 Survival analysis of patients with PMMEUnivariate analysis showed that gender,family history of tumor,general type,lymph node and incisional margin were the influencing factors of survival.The results of multivariate analysis showed that:gender(female)P=0.019,HR=0.216(0.060-0.780);tumor family history(positive)P=0.002,HR=5.675(1.904-16.910).In summary,male and family history of tumors are independent risk factor that affect the survival of PMME patients.3.3 Analysis of mutation difference of TP53 in PMME and ESCCTP53 mutation occurred in 2 of 15 PMME samples,and the mutation frequency was 13.3%.There were two specific loci,rs1057520007 and rs1042522,respectively.The two SNPs with mutation were all missense mutations.Among 33 ESCC samples,25 had TP53 mutation,the mutation frequency was 75.6%,30 mutation events were detected.Among the 23 SNP changes,missense mutation was 69.6%(16/23),nonsense mutation was 21.7%(5/23),splice site mutation was 8.7%(2/23),deletion and insertion of 7 cases were all frameshift mutations.Chi square test was used to evaluate the mutation of TP53 in PMME and ESCC,the difference was statistically significant(chi square=16.319,P<0.001),the mutation frequency of TP53 in ESCC was higher than that in PMME.3.4 Association analysis of TP53 mutation with clinicopathological characteristics of PMME and ESCCTwo cases of TP53 mutation in PMME group were all male patients younger than 60 years old.The frequency of TP53 mutation was 90.0%(17/21)in men and 66.7%(8/12)in women in ESCC group,and there was no difference between men and women(P=0.420).The mutation rate of TP53 was 100%(9/9)in the age group<60 years old and 66.7%(16/24)in the age group? 60 years old.There was no significant difference among the upper,middle and lower thoracic segments(P=0.806).The mutation rate of TP53 was 66.7%(12/18)in lymph node negative group and 86.7%(13/15)in lymph node positive group.There was no difference between the two groups(P=0.242).There was no significant difference between TP53 mutation and clinicopathological features(gender,age,family history,smoking history,drinking history,tumor location,invasion degree,lymph node metastasis,tumor length and diameter,TNM stage,et al).3.5 TP53 mutation and survival of PMME and ESCC patientsIn this study,15 PMME patients were followed up successfully.The survival time of 2 patients with TP53 mutation was 0.6 and 0.7 years,respectively.Kaplan-Meier analysis showed that there was no difference between the two groups(P=0.194).In 33 ESCC patients,the 5-year survival rate of T53 mutation group was 19.2%,and that of non-mutation group was 60%.Compared with the mutation group,the non-mutation group had a better survival trend(P=0.090).In general,TP53 mutation had no effect on the survival of PMME and ESCC patients.4 Conclusions?PMME is very rare(0.08%,210/250000)and more likely to occur in men than in women(male:female=3.1:1);the tumors are more frequent in the lower thoracic segment,the second in the middle thoracic segment,the least in the cervical and upper thoracic segments,and the most common symptom is dysphagia?Male and tumor family history positive are independent risk factors for the survival of PMME patients.?The mutation frequency of TP53 was lower in PMME than in ESCC.TP53 mutation had no significant effect on the survival of PMME/ESCC patients.