| Background and objectiveNeuroendocrine neoplasms(neuroendocrine neoplasms,NENs)are a kind of heterogeneous tumors originating from neuroendocrine cells.The biological behavior of neuroendocrine neoplasms can be divided into highly differentiated neuroendocrine tumor(neuroendocrine tumor,NET)and poorly differentiated neuroendocrine carcinoma(neuroendocrine carcinoma,NEC).The most common sites are gastrointestinal,pancreas and lung.With the improvement of imaging technology and pathological diagnosis,the diagnosis rate of NENs has increased significantly in recent years,which makes clinicians pay more and more attention to the disease.Correct diagnosis is essential for the treatment of NENs because their clinical and biological heterogeneity is related to treatment response and prognosis.Immunohistochemistry is an indispensable tool for pathologists to correctly diagnose,classify and grade these diseases.When the morphological features were suspected to be NENs,the diagnosis should be confirmed by immunohistochemical staining of neuroendocrine markers such as synaptophysin(synaptophy sin,Syn)and chromagranin A(chromogranin A CgA),and the proliferative activity was evaluated by mitosis and Ki-67 to determine the classification and grading.Somatostatin receptor 2(somatostatin receptor 2,SSTR2)is a subtype of somatostatin receptor,and somatostatin has the highest affinity to SSTR2.Based on this principle,the expression of SSTR2 is the basis of somatostatin receptor functional imaging and somatostatin analogue therapy.SSTR2 is usually highly expressed in well-differentiated NET and has shown an independent prognostic role in gastrointestinal and pancreatic NENs.As a tumor suppressor gene,P53 is one of the most frequently mutated genes in malignant tumors.With regard to the classification of high-grade NENs,WHO puts more emphasis on the change of molecular typing.The expression of p53 protein evaluated by immunohistochemistry reflects the potential P53 mutation state of the tumor and plays an important role in the diagnosis and prognosis of NENs.At present,there is no specific immunohistochemical method that can independently confirm the diagnosis of NENs.In clinical work,several kinds of immunohistochemical comprehensive diagnosis are usually used.In this study,the clinicopathological data of 237 cases of digestive system NENs and 184 cases of respiratory system NENs were collected,and the expression of SSTR2 and p53 in digestive and respiratory system NENs was analyzed.To explore the clinicopathological features of NENs in different anatomic sites,so as to provide a more effective basis for standardized pathological classification and clinical diagnosis and treatment.Methods1.The digestive and respiratory NENs,diagnosed in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were collected,including 237 cases of digestive system and 184 cases of respiratory system.All cases were confirmed according to the diagnostic classification criteria of WHO NENs and confirmed by two pathologists according to the morphological characteristics of HE and the positive results of the following immunohistochemical markers(Syn,CgA,Ki-67).The clinicopathological data of all cases were accessed through the electronic medical record system,including sex,age,tumor location,tumor differentiation,tumor grade,related immunohistochemical results and so on.2.Immunohistochemical method was used to detect the expression of SSTR2 antibody in 216 cases of NETs and p53 antibody in 205 cases of NEC.3.SPSS21.0 statistical software was used for data analysis.The count data of clinicopathological features were expressed as n(%).χ2 test was used for comparison between groups.Fisher test was performed for data with n<40 or theoretical frequency T<5.Spearman correlation analysis was used to test the correlation.The difference was statistically significant(P<0.05).Results1.Among the 237 cases of digestive system NENs,all cases were analyzed and compared according to the tumor’s primary site.The incidence of NENs in different parts is different.There are 22 cases of esophagus(9.3%,22/237),93 cases of stomach(39.2%,93/237),14 cases of small intestine(5.9%,14/237),and 59 cases of colorectal(24.9%,59/237),1 case of appendix(0.4%,1/237),44 cases of pancreas(18.6%,44/237),and 4 cases of gallbladder(1.7%,4/237).According to statistical analysis,there are differences in the pathological grades of NENs in different parts(P<0.05).The esophagus is all NEC(100.0%,22/22),the stomach is mainly NEC(66.7%,62/93),and the small intestine is mainly NEC(42.8%,6/14),NET G1(66.1%,39/59)in the colorectum,NET G1 in the appendix(100.0%,1/1),and NET G2 in the pancreas(50.0%,22/44),NEC is mainly in the gallbladder(75.0%,3/4).2.Among the 184 cases of respiratory NENS,155 cases were lung and 29 cases were mediastinum.Statistical analysis showed that the pathological grade of NENS in different sites was different(P<0.05).The main NENS in lung was SCNEC(46.5%,72/155),and the main NENS in mediastinum was atypical carcinoid(89.7%,26/29).3.Among the 237 cases of digestive system NENs,the positive rate of Syn was 100%,and the positive rate of CgA was 62.9%.According to statistical analysis,there are differences in the expression of CgA in different parts and pathological grades(P<0.05),the positive expression rate in the esophagus is the lowest,and the positive rate in NETs is higher than that in NEC.4.The positive rates of Syn and CgA were 89.7%and 52.7%in 184 cases of respiratory NENS.The positive rates of Syn and CgA in mediastinum were higher than those in lung.According to statistical analysis,there are differences in the expression of Syn and CgA in different pathological grades(P<0.05).The positive rates in typical and atypical carcinoids are higher than those in NEC,and the positive rates in SCNEC are higher than those in LCNEC.5.In 126 cases of digestive system NETs,the expression of SSTR2 was as follows:4.8%(6/126)negative expression,0.8%(1/126)weak positive expression,2.4%(3/126)moderate positive expression,92.0%(116)/126)Strong positive expression.In 90 cases of respiratory NETs,the expression of SSTR2 was as follows:65.6%(59/90)negative expression,2.2%(2/90)weak positive expression,11.1%(10/90)moderate positive expression,21.1%(19/90)Strong positive expression.There were differences in the expression of SSTR2 in the digestive and respiratory NETs,with strong positive expression in the digestive system and negative expression in the respiratory system(P<0.05).6.Spearman correlation analysis showed that the positive expression of SSTR2 in digestive NETs was negatively correlated with pathological grade(r=-0.266,P<0.05),and the positive expression was higher in G1 and G2.7.In 111 cases of digestive system NEC,the expression of P53 was as follows:52.3%(58/111)negative expression,47.7%(53/111)positive expression.In 94 cases of respiratory system NEC,the expression of P53 is as follows:17.0%(16/94)negative expression,83.0%(78/94)positive expression.There are differences in the expression of P53 in digestive and respiratory NEC.Most of the respiratory system NEC is mutant,and the digestive system NEC is mostly wild type(P<0.05).The results of Spearman correlation analysis showed that the expression of P53 and Ki-67 was positively correlated in the digestive and respiratory system NEC(r=0.155,P<0.05).Conclusions1.There are differences in the pathological characteristics of NENs in different anatomical parts.The esophagus and lungs are mainly poorly differentiated NECs.The colorectal,pancreas,and mediastinum are mostly well-differentiated NETs;CgA is more positively expressed in the stomach,small intestine,pancreas,and mediastinum.2.The degree of positive expression of SSTR2 in NETs originating in the digestive system was significantly higher than that in NETs originating in the respiratory system,suggesting that the expression of SSTR2 in digestive system NETs is more specific;in digestive system NETs,the degree of positive expression of SSTR2 is similar to that of NETs in the respiratory system.The pathological grade is negatively correlated,indicating that SSTR2 is related to its prognosis.3.The mutation rate of P53 in respiratory system NEC is higher than that in digestive system NEC.In NEC,P53 mutation and Ki-67 proliferation index are positively correlated. |
