The Association Of Neuroendocrine Differentiation With Progression And Prognosis Of Gastrointestinal Adenocarcioma And Neuroendocrine Carcinoma

Objective:To investigate the effects of different proportions of neuroendocrine differentiation components on clinicopathological characteristics,progression and prognosis of gastrointestinal adenocarcinoma and neuroendocrine carcinoma.And to explore the expression and clinical significance of Secretagogin(SCGN)as a novel neuroendocrine marker.Methods:The clinicopatholihical data of 122 cases of gastrointestinal malignant tumors,including 36 cases of adenocarcinoma,30 cases of adenocarcinoma with neuroendocrine differentiation,20 cases of mixed adenoendocrine carcinoma(MANEC)and 20 cases of neuroendocrine carcinoma were collected from the Affiliated Hospital of Qingdao University from 2011 to 2017.Immunohistochemistry was used to detect the expression of SCGN in paraffin sections of these tumor tissues.In addition to the collected clinicopathological data,these patients were followed up for a survival analysis.SPSS 22.0 software was used for statistical analysis.Comparison between reference groups was conducted by chi-square test.Univariate survival analysis was performed by kaplan-meier method and log-rank test,and multivariate survival analysis was performed by Cox regression.When P<0.05,the difference was statistically significant.Results:(1)The differences about nerve infiltrating of the four groups have the statistically significant,(?~2=9.101,P<0.05),in which adenocarcinoma group have more nerve invasion cases,at 61.1%,followed by MANEC group(55.0%)and adenocarcinoma with neuroendocrine differentiation group(53.3%),lower for NEC group(27.8%).Further analysis showed that the incidence of nerve invasion in adenocarcinoma group was higher than that in NEC group.The clinicopathological characteristics such as age,gender of four groups have no obvious differences.(2)In this study,the average survival time of four groups was(57.367±3.607)months,and the median survival time was 54 months.The average survival time of NEC group,MANEC group,adenocarcinoma with NED group and adenocarcinoma were(41.067±6.804)months,(56.219±8.450)months,(61.296±6.292)months,(68.118±6.009)months,respectively.Survival analysis showed that the survival distribution of four groups of gastrointestinal malignant tumors had significant difference(?~2=14.174,P<0.05).Therefore,we grouped the patient into two groups using 30%NED as a cut off.Survival analysis showed that the prognosis of patients with?30%NED is poor.(?~2=8.884,P<0.05).The TNM stage(P=0.027,HR=0.218,95%CI:0.057~0.843)and presence of distant metastasis(P=0.028,HR=2.043,95%CI:1.079~3.867)were independent prognostic factors.(3)It showed high level SCGN expression in 38.9%of NEC,30.6%of adenocarcinoma,30.0%of MANEC and 3.3%of adenocarcinoma with neuroendocrine differentiation.The difference was statistically significant(?~2=11.605,P<0.05).This revealed that SCGN was highly expressed in NEC,adenocarcinoma and MANEC,but poorly expressed in adenocarcinoma with neuroendocrine differentiation.The expression of SCGN in the four groups of gastrointestinal malignancies was correlated with tumor size(?~2=6.342,P<0.05),invasion depth(?~2=4.646,P<0.05),and distant metastasis(?~2=4.051,P<0.05).(4)65.6%patients of secretagogin-strong-positive subgroup were dead.There is no significant statistical difference with secretagogin-poor-positive subgroup which is 8.9%.Conclusions:(1)The survival distribution of gastrointestinal malignant tumors in the four groups with different proportion of neuroendocrine components was significantly different.The prognosis of NEC was worse than that of adenocarcinoma.The cumulative survival rates of NEC,MANEC,adenocarcinoma with NED and adenocarcinoma decreased gradually.It is suggested that the higher the proportion of neuroendocrine components in tumor tissue,the worse the prognosis of patients.Neuroendocrine differentiation is an unfavorable factor for the prognosis of gastrointestinal adenocarcinoma and NEC.(2)The expression of SCGN in gastrointestinal adenocarcinoma had no significantly difference from that in NEC and MANEC.It is suggested that SCGN may not be highly specific as a neuroendocrine marker.SCGN expression in adenocarcinoma with NED was lower than that in NEC and MANEC.It is suggested that the expression of SCGN in neuroendocrine tumors may be related to the proportion of neuroendocrine differentiation.The expression of SCGN may be lower in tumors with low proportion of neuroendocrine components.(3)SCGN may be involved in the formation and infiltration of gastrointestinal tumors.Strong expression of SCGN may indicate deeper invasion,but it is not significantly correlated with the prognosis of tumor patients.