Comparative Study On The Clinicopathological Features And Prognosis Of Neuroendocrine Tumors Of Breast And Gastrointestinal Tract

Objective:This study aims to explore whether there are differences between breast and gastrointestinal neuroendocrine tumors in gender,age,tumor size,number of tumors,histopathological morphology,histopathological classification and prognosis,so as to provide theoretical basis for the diagnosis and prognosis of breast and gastrointestinal neuroendocrine tumorsMethods:1)Forty cases of breast NET and 122 cases of gastrointestinal NEN were selected from the Department of Pathology,Qilu Hospital,Shandong University and the Department of Pathology,Kingmed Diagnosis in Jinan from 2007 to 2016.No preoperative chemotherapy,radiotherapy and immunotherapy were given.Tumor staging refers to the 7th edition of TNM staging developed by the International Union Against Cancer and the American Joint Committee on Cancer.2)The selected cases were re-examined,including HE sections and immunohistochemical sections.The diagnosis of breast NET refers to WHO Classification of Breast Tumors(2012,4th Edition)and Breast Pathological Diagnosis and Differential Diagnosis(Huaye Ding.Xiangsheng Zhang,etc.).Breast NET was divided into highly differentiated neuroendocrine tumors(primary carcinoid of the breast),large cell neuroendocrine carcinomas,small cell neuroendocrine carcinomas,neuroendocrine ductal carcinoma in situ(spindle cell neuroendocrine carcinomas of the breast),non-specific invasive carcinomas with neuroendocrine differentiation,solid papillary carcinomas and cell-rich mucinous carcinomas.The first four require CgA and Syn to be diffuse positive,while the latter three require more than 50%of CgA and Syn positive cells.The diagnostic criteria of gastrointestinal NET are strictly based on the Chinese Consensus on Pathological Diagnosis of Gastrointestinal Pancreatic Neuroendocrine Tumors(2013 edition).Histological classification of gastrointestinal neuroendocrine tumors includes NET G1,NET G2,highly proliferative NET,neuroendocrine carcinoma and mixed gonad neuroendocrine carcinoma.3)Statistical Processing SAS9.4 statistical software was used for data analysis.χ2 test for comparison of multigroup rates,Spearman rank correlation method was used for correlation analysis.Survival curve using Kaplan-Meier method.The COX risk proportional regression model was used for multivariate survival analysis.The difference was statistically significant with P<0.05.Results:1)There was no significant difference in the expression of CgA and Syn in breast NET and gastrointestinal NET(P>0.05).2)There were statistical differences between breast and gastrointestinal NET in sex,tumor size,number of tumors,mitosis,Ki-67index,histological morphology and clinical stage(P<0.05).NET in breast occurs in women.Tumor size is small,multiple lesions account for a certain proportion,mitotic number is small,Ki-67 index is low,There are many histological forms.The clinical stage is low.The male-to-female ratio of gastrointestinal NEN was 1.98:1.Tumor volume was larger,the number of tumors was more single,the number of mitosis was more,and Ki-67 index was higher.The clinical stage is high.3)Common factors affecting the survival of breast and gastrointestinal NET include nerve invasion,clinical stage,Ki-67 index,metastasis and tumor size.Nerve invasion,late clinical stage,high Ki-67 index,metastasis and large tumor volume suggest poor prognosis.Mitosis(per 10 HPF)is not a factor affecting the survival of breast NET,However,in gastrointestinal NET,the more mitosis(per 10HPF),the worse the prognosis.4)Histological classification of breast neuroendocrine tumors was no correlation with metastasis,tumor size,vascular invasion,nerve invasion,clinical stage and survival time(P>0.05).In gastrointestinal neuroendocrine tumors,NET G1 and NET G2 cases,tumors are small in size,with few mitosis,rare vascular infiltration and nerve invasion,early clinical stage,long survival time and high survival rate.Neuroendocrine and mixed gland neuroendocrine carcinomas have large tumors,more mitosis,common vascular infiltration and nerve invasion,late clinical stage,short survival time and low survival rate.The prognostic indicators of high proliferative activity NET were between NET(G1+G2),neuroendocrine carcinoma + mixed gonad neuroendocrine carcinoma.5)In the long run,breast NET has longer survival time and lower mortality than gastrointestinal NET.6)Survival curve analysis of breast neuroendocrine tumors showed that:Highly differentiated neuroendocrine tumor,neuromucinous carcinoma(The number of CgA and Syn positive cells was more than 50%.),solid papillary carcinoma(The number of CgA and Syn positive cells was more than 50%.)and neuroendocrine carcinoma in situ have better prognosis.The prognosis of large cell neuroendocrine carcinoma.small cell neuroendocrine carcinoma,non-specific invasive carcinoma with neuroendocrine differentiation(The number of CgA and Syn positive cells was more than 50%.)is poor.7)Gastrointestinal NET(G1 + G2)has longer survival time and lower mortality.The biological behavior of highly proliferative NET is different from that of NET(G1+G2)and neuroendocrine carcinomas.The long-term survival rate was between NET and neuroendocrine carcinomas.8)The number of mitotic figures(number/1 OHPF)in gastrointestinal NET was positively correlated with Ki-67(P<0001).There was no significant correlation between the number of mitotic figures and Ki-67 in breast NET.With the help of digital slice scanning system,the interpretation of Ki-67 positive cells can be objective and accurate.Conclusions:1)The same as the neuroendocrine tumors,NET in breast and gastrointestinal tract differs greatly in sex,tumor size,number of tumors,mitosis,Ki-67 index,histological morphology and clinical stage.2)The number of mitosis(number/10HPF)is not related to the prognosis of breast NET.However,it was positively correlated with the prognosis of gastrointestinal NET.3)Histological classification of gastrointestinal NET is better than that of breast NET in reflecting its biological behavior.4)In the long run,breast NET has longer survival time and lower mortality than gastrointestinal NET.5)In breast neuroendocrine tumors,The prognosis of highly differentiated neuroendocrine tumor、cell-rich mucinous carcinoma and solid papillary carcinoma(Both of them require CgA and Syn positive cells to be more than 50%.)、neuroendocrine ductal carcinoma in situ(spindle cell neuroendocrine carcinoma)was significantly better than that of other histological types.6)Gastrointestinal NET(G1 + G2)has longer survival time and lower mortality.The biological behavior of highly proliferative NET is different from that of NET(G1+G2)and neuroendocrine carcinomas.The long-term survival rate was between NET(G1-G2)and neuroendocrine carcinomas.7)The number of mitotic figures(number/10HPF)in gastrointestinal NET was positively correlated with Ki-67(P<0001).There was no significant correlation between the number of mitotic figures and Ki-67 in breast NET.