Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases

BackgroundMixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined.AimsTo present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC.Materials and methodsThe clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, β-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed.ResultsAll of the cases showed microsatellite stable status, expressed E-cadherin and membrane β-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum.ConclusionsGastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.     

Expression of HBME-1 and CD56 in follicular variant of papillary carcinoma in children: An immunohistochemical study and their diagnostic utility

Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer in children; and the follicular variant is the second most common variant after the classic subtype. The histological appearance of follicular variant of papillary thyroid cancer (FVPTC), can be mimicked by benign follicular nodules. Pediatric pathologists encountering such lesions with FVPTC-like appearance may err on diagnosing the benign lesions as malignant. In adult patients, several immunohistochemical markers have emerged recently as a useful adjunct to distinguish differentiated thyroid carcinomas from benign follicular lesions. We undertook an inter-institutional retrospective study to establish the diagnostic utility of immunohistochemical staining for HBME-1, Galectin-3 and CD56 in differentiating FVPTC from its benign mimics, follicular adenoma and adenomatoid nodules, in children. Our specific aim of the project was to define the sensitivity and specificity of the three antibodies in FVPTC. Based on institutional diagnoses, a total of 66 cases were obtained: 32 FVPTC and 34 benign follicular nodules that comprised of 23 follicular adenoma and 11 adenomatoid nodules. Five investigators, who were blinded to the original diagnoses, independently reviewed the slides following pre-determined criteria and semi-quantitatively scoring the immunohistochemical staining. The immunohistochemical staining revealed that a combination of positive HBME-1 and negative CD56 result gave 100% specificity and positive predictive value in distinguishing FVPTC from benign follicular nodules. However, the antibody combination suffered from a lower sensitivity (50%). We used a cutoff of 25% positivity of tumor cells in determining positivity of tumor cells to an antibody. In conclusion, our study found a very high specificity and strong positive predictive value for the combination of HBME-1 and CD56 immunohistochemical stains in distinguishing FVPTC from benign follicular lesions.     

Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer

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膜辅助蛋白CD46 rs1970530遗传变异对肝癌发病风险的影响

背景与目的：膜辅助蛋白CD46可保护宿主细胞免受补体依赖的细胞毒性作用，研究表明，CD46可能作为肝细胞癌（hepatocellular carcinoma，HCC）患者的潜在生物标志物。探讨CD46基因表达及启动子区遗传变异与HCC发病风险的关系。方法：通过基因表达谱交互分析（gene expression profiling interactive analysis，GEPIA）在线网站分析HCC组织和正常肝组织CD46表达的差异；2011—2015年在华北理工大学附属唐山市工人医院和华北理工大学附属唐山市人民医院经病理学检查确诊且未经放化疗的240例HCC患者作为病例组，对照组为同时期入院体检的500名健康人群。采用聚合酶链反应-限制性片段长度多态性分析（polymerase chain reaction-restriction fragment length polymorphism，PCR-RFLP）法进行基因分型，检测两组基因型频率和等位基因频率，评估CD46 rs1970530遗传变异与HCC发病风险的关系。结果：CD46在HCC组织与正常组织中的表达差异有统计学意义（P<0.05）。经非条件logistic回归分析发现，CD46 rs1970530至少携带一个G等位基因型在病例组及对照组之间差异有统计学意义（OR=0.666，95% CI：0.448~0.990，P<0.05）；两组间等位基因G频率差异有统计学意义（OR=0.689，95% CI：0.478~0.994，P<0.05）。分层分析结果显示，至少携带一个G等位基因者可降低高年龄组（>60岁）（P=0.048）和男性（P=0.023）人群的HCC发病风险，在女性和低年龄组（≤60岁）中差异无统计学意义（P>0.05）。按吸烟状态进行分层分析，rs1970530变异与HCC易感性无明显关联（P>0.05）。结论：HCC中CD46基因高表达及CD46 rs1970530遗传变异影响HCC发病风险。