解放军医学杂志2024，Vol.49Issue(3)：288-296,9.DOI:10.11855/j.issn.0577-7402.1494.2023.0427
PNEC和GABA在肺神经内分泌肿瘤中的作用
Role of PNEC and GABA in pulmonary neuroendocrine tumors
摘要
Abstract
Objective To investigate the role of pulmonary neuroendocrine cells(PNEC)and γ-aminobutyric acid(GABA)in patients with pulmonary neuroendocrine tumors(PNET).Methods The pathological specimens of 29 cases of PNET treated in the eighth Medical Center of Chinese PLA General Hospital from October 2018 to January 2022 were collected.The morphological characteristics were observed by HE staining,and the expression levels of synaptophysin(Syn),chromogranin A(CgA),CD56,Ki-67,CD86 and CD163 were observed by immunohistochemical staining.Calcitonin gene-related peptide(CGRP)and glutamic acid decarboxylase(GAD)65/67 in different types of PNETs were detected by double antibody immunofluorescence co-staining,and the correlation between GAD65/67 positive PNEC and macrophage polarization was analyzed.Results The results of HE staining showed that all four types of PNET tissues had neuroendocrine(NE)characteristics:rosette structure and organ nesting or palisade pattern,but they were different,and the proportion of mitotic cells from low to high was typical carcinoid(TC),atypical carcinoid(AC),large cell neuroendocrine carcinoma(LCNEC)and small cell lung cancer(SCLC).The results of immunohistochemical staining showed that the positive expression rate of Syn and CgA and the positive degree of Syn,CgA and CD56 in carcinoid(TC and AC)were significantly higher than those in LCNEC and SCLC(P＜0.05).The Ki-67 indices of the four types of PNET are:TC＜5%,AC 5%-20%,LCNEC and SCLC＞75%respectively.The number of PNEC in carcinoid was significantly higher than that in LCNEC,SCLC and paratumoral tissues(P＜0.05),but there was no significant difference in the number of PNEC between LCNEC and SCLC and para-tumor tissues(P＞0.05).The results of immunofluorescence staining showed that the number of GAD65/67 positive cells co-expressing GAD65/67 in 95%PNEC was significantly higher than that in LCNEC,SCLC and para-tumor tissues(P＜0.05),but there was no significant difference between LCNEC and SCLC GAD65/67 positive cells and para-tumor tissues(P＞0.05).The results of immunohistochemical staining also showed that the number of CD86 positive M1 macrophages was significantly higher than that of CD163 positive M2 macrophages in para-tumor tissues(P＜0.05),while M2 macrophages were significantly more than M1 macrophages in AC,LCNEC and SCLC(P＜0.01).Correlation analysis showed that the number of GAD65/67 positive PNEC cells in PNET was negatively correlated with the number of CD163 positive M2 macrophages in tumor stroma(r=-0.6336,P=0.0174).Conclusions PNEC is the main source of GABA in lung tissue and plays an immunomodulatory role in the lung,which may be involved in the progression of PNET.关键词
肺神经内分泌细胞/γ-氨基丁酸/巨噬细胞/肺神经内分泌肿瘤Key words
pulmonary neuroendocrine cell/γ-aminobutyric acid/macrophage/pulmonary neuroendocrine tumor分类
医药卫生引用本文复制引用
赵小琼,陈文,孙玉洁,蔺晨雨,岳渊,李蕊,张涛,肖漓..PNEC和GABA在肺神经内分泌肿瘤中的作用[J].解放军医学杂志,2024,49(3):288-296,9.基金项目
This work was supported by the Project of Military Medical Science and Technology Youth Cultivation Plan(18QNP035),and the Project of Heilongjiang Provincial Health Commission(20210202040058) 军队医学科技青年培育计划项目(18QNP035) （18QNP035）
黑龙江省卫健委立项课题(20210202040058) （20210202040058）
