Analysis Of Clinicopathologic Features Of Cervical Neuroendocrine Tumor

Objective:To investigate the clinicopathologic features of cervical neuroendocrine tumor and analyze the survival and prognostic factors of the patients To analyze the sensitivity and specificity of the novel neuroendocrine marker IN SM1 and four traditional neuroendocrine markers which including Syn,CgA,CD56 and NSE in the pathological diagnosis of cervical neuroendocrine tumor,and to explore the diagnostic value of INSM1 in cervical neuroendocrine tumor.Methods:A retrospective analysis was performed on the patients with cervical neuroendocrine tumor who were firstly diagnosed in yunnan cancer center from January 1,2010 to December 31,2017.Descriptive analysis and survival analysis were performed on the relevant factors to analyze their clinical characteristics,survival status and prognostic factors.The pathological tissue samples of 37 cases of cervical neuroendocrine tumor and 44 cases of cervical non-neuroendocrine tumor with pathological tissue samples in our hospital were screened.The expressions of INSMI1,Syn,CgA,CD56 and NSE were detected by immunohistochemical staining,and the sensitivity and specificity of each immunohistochemical marker were analyzed.Results:1.Descriptive analysisThe average age of 73 patients with cervical neuroendocrine tumor was 43.88±11.225 years.The pathological types were mainly small cell neuroendocrine carcinoma,with 45 cases(61.6%),5 cases(6.8%)of large cell neuroendocrine carcinoma,2 cases(2.7%)of atypical carcinoid carcinoma,21 cases(28.8%)of neuroendocrine carcinoma without specific classification.The most common clinical manifestations were irregular vaginal bleeding(63.0%),Contact vaginal bleeding(38.4%)and abdominal pain(30.1%).57(78.1%)patients were infected with HPV,11(15.1%)patients were not infected,and 5(6.8%)patients had unknown HPV infection status.Lymph node(19.2%),lung(4.1%),bone(4.1%)and liver(2.7%)were the most common metastatic sites.Stage Ⅰ(63.0%)and stage Ⅲ(17.8%)were the most common.The main treatment methods were surgery+chemoradiotherapy(26.0%),surgery+chemoradiotherapy(19.2%),chemotherapy(15.1%)and chemoradiotherapy(12.3%).Lung metastasis(11.0%)and liver metastasis(8.2%)were the most common recurrent metastases.2.Survival analysis2.1 Overall survival analysisThe survival analysis of 73 patients with cervical neuroendocrine carcinoma showed that the 1-year,2-year and 3-year survival rates were 83.56%,72.6%and 70.0%,respectively,with a median survival period of 8.26 years.2.2 Kaplan-meier univariate analysisThrough the Kaplan-meier univariate analysis,it is concluded that the following factors have a significant impact on survival prognosis in patients with cervical neuroendocrine carcinoma,including FIGO stage(P=0.001),tumor size(P=0.028),early surgery(P=0.033),Whether there is metastasis at the time of diagnosis(P=0.002),recurrence and metastasis(P=0.001),NSE(P=0.039),SCC(P=0.043),and LDH(P=0.000),Ca2+(P=0.028),osmotic pressure(=0.037).2.3 COX regression multivariate analysisThe factors with P<0.05 in the single factors analysis were brought into the COX regression multivariate analysis,it is concluded that the factors that have a significant impact on the survival prognosis of cervical neuroendocrine cancer include metastasis at the first diagnosis(RR is 2.528,P=0.040),recurrence and metastasis(RR is 3.552,P=0.002),surgery(RR is 0.360,P=0.030),and LDH increased(RR is 4.056,P=0.009).3.Pathological features analysisIn 37 cases of cervical neuroendocrine tumors,the positive rate of INSM1 was 91.9%(34/37),while the Syn,CgA,CD56 and NSE was 89.2%(33/37),70.3%(26/37),81.1%(30/37)and 67.6%(25/37),respectively,and the positive rate of INSMI,Syn,CgA,CD56 and NSE in cervical non-neuroendocrine tumor is 0%(0/44),0%(0/44),and 0%(0/44),15.9%(7/44)and 9.1%(4/44)respectively.The sensitivity of INSM1 to the differentiation diagnosis of cervical neuroendocrine tumor was 91.9%,and the specificity was 100%.The sensitivity of Syn,CgA,CD56 and NSE in the diagnosis of cervical neuroendocrine tumor was 89.2%,70.3%,81.1%and 67.6%,respectively,and the specificity was 100%,100%,84.1%and 90.9%,respectively.Comparing INSM1 as a novel neuroendocrine marker with four traditional neuroendocrine markers as a whole,the results showed that INSM1’s sensitivity to all neuroendocrine tumors(91.9%)was slightly lower than that of the traditional neuroendocrine marker group(97.3%)However,in terms of specificity,the INSM1 group(100%)is significantly better than the traditional neuroendocrine marker group(77.3%).Conclusions:1.Cervical neuroendocrine tumors are malignant tumors with a very low incidence.Among all cervical malignant tumors diagnosed in Yunnan Provincial Cancer Hospital from 2010 to 2017,they accounted for 0.95%(79/8342).2.Kaplan-Meier univariate analysis showed that tumor markers NSE,SCC,and biochemical indicators LDH,Ca2+,and osmotic pressure were related to the prognosis of patients.3.INSM1 is a reliable marker for differentiation of cervical neuroendocrine tumor,which is highly sensitive and specific compared with traditional neuroendocrine markers.