The Relevance Study Of Proteins Expression And Their Clinicopathological Characteristics In Gastroenteropancreatic Neuroendocrine Neoplasms

Background and objective:Neuroendocrine neoplasms are a group of heterogeneous tumors derived from the peptidergic neurons and neuroendocrine cells,which can be raised in many systems.Of which,gastroenteropancreatic neuroendocrine neoplasms are the most common ones.The incidence of neuroendocrine neoplasms has increased in recent years,and the therapeutic effect is not satisfactory.The correlation between the proteins expression and thetherapeutic effect and prognosis is far fromclear.Therefore,we detected the expression of various antibodies in gastroenteropancreatic neuroendocrine neoplasms to study the relationship between proteins expression and clinicopathological features,to get understand the molecular biological changes of gastroenteropancreatic neuroendocrine neoplasms,and to provide theoretical basis for more standardized and effective clinical diagnostic methods and treatments.Methods:A total of 91 cases of gastroenteropancreatic neuroendocrine neoplasms were collected from January 2010 to December 2015 in Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College.Tumor tissue was selected to make tissue chips for HE staining and immunohistochemical staining of CK7,TTF-1,CK20,CDX2,p53,Rb,SSTR-2,MLH1,MSH2,MSH6,PMS2,BRAF V600E,MGMT,AFP,PD-1,PD-L1,and Ki-67.The relationship between proteins expression and clinicopathological features of gastroenteropancreatic neuroendocrine neoplasms,such as grade,location,and so on,was analyzed.RESULTS:1.Complete clinical data are available for these 91 cases of gastroenteropancreatic neuroendocrine neoplasms,and grouped them according to pathological classification(NET G1,G2,G3 and NEC),including 5 cases of NET G1(5.49%),16 cases of NET G2(17.58%),4 cases of NET G3(4.39%),and 66 cases of NEC 66 cases(72.53%).2.Clinicopathological characteristics:The difference between the age,gender,and different pathological classification groups(NET G1,G2,G3,NEC)in tumor patients is statistically significant,and the classification of tumors is related to gender and age(P<0.01);The difference between clinicopathological features such as the original site of the tumor,the presence of vascular tumor suppository and nerve invasion,the presence of lymph node metastasis and distant metastasis,and the different pathological classification groups(NET G1,G2,G3,NEC)is statistically significant.There was a correlation between tumor classification and clinicopathologic characteristics(P<0.05).3.17 immunohistochemical results showed:tumor classification(NET G1,G2,G3,and NEC)was related to the expression of CDX2,P53,Rb,SSTR-2,and Ki-67(P<0.05);but no significant correlation with the expression of other antibodies(P>0.05).The primary site of the tumor(esophagogastric junction,stomach,rectum,liver and gallbladder,pancreas,and other parts)was correlated with the expression of P53,Rb,SSTR-2,MGMT,and Ki-67(P<0.05);but no significant correlation with the expression of other antibodies(P>0.05).BRAF V600E and AFP were negative in all gastrointestinal pancreatic endocrine tumors;the positive expression rate of PD-1 and PD-L1 in gastrointestinal pancreatic endocrine tumors was low,with only 5 cases of positive expressions(5.4%)in PD-1 and 8 positive expressions(8.7%)in PD-L1.MLH1,MSH2,MSH6,and PMS2 showed lower in gastroenteropancreatic neuroendocrine neoplasms,of which MLH1 was negative in 3 cases(3.2%),MSH2 was negative in 2 cases(2.1%),and MSH6 was negative in 3 cases(3.2%),There were 4 negative cases(4.3%)of PMS2.4.P53 was expressed in no NET G1,weekly to moderately positive expression in G2 and G3,and strongly positive expression of P53 only appeared in NEC(P = 0.013).The positive expression rate of CDX2 in NEC was significantly higher than that of other grading groups,and the difference was significant(P = 0.007).Rb was negative in NET G1,G2,and G3,and the positive expression rate in NEC was significantly higher than that of other grading groups,and the difference was significant(P<0.001).The strong positive expression rate of SSTR-2 in NET G1 and G2 was significantly higher than that of NEC,and the difference was significant(P<0.001).5.The expression rate of P53 was significantly higher than that of other primary sites in the cases of esophagogastric junction,stomach,liver and gallbladder,and the difference was significant(P=0.002).The expression rate of Rb was significantly higher than that of other primary sites in cases of primary esophagogastric junction,stomach and colorectal tumors(P = 0.001).The expression rate of SSTR-2 was significantly higher in primary tumors in liver and gallbladder,pancreas than in other primary sites,and the difference was significant(P<0.001).The expression rate of MGMT was significantly higher than that of tumors in other primary sites in the esophagogastric junction,stomach,liver,gallbladder,and the difference was significant(P = 0.005).Conclusion:1.The older the patient is,the higher the classification of the tumor may be.With the increase of tumor classification,the risk of vascular tumor suppository,nerve invasion,lymph node metastasis,and distant metastasis increased,and the prognosis was correspondingly poor.2.P53,CDX2,Rb,ki-67 have a higher positive rate in NEC and can be used as NEC markers.TTF1 and CDX2 are of reference value when judging the source of tumors with unknown primary lesions.3.The strongly positive expression rate of SSTR-2 in NET G1 and G2 was higher than that of NEC.4.The expression of PD-1 and PD-L1 in neuroendocrine tumors is low,and the immunotherapy of PD-1/PD-L1 has limited effect in the treatment of NEN.5.The negative expression of BRAF V600E indicates that it has not played an important role in the development of NEN.