Manne Ashish, Esnakula Ashwini, Abushahin Laith, Tsung Allan
Department of Internal Medicine, Division of Medical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Cancers (Basel). 2021 Jun 19;13(12):3059. doi: 10.3390/cancers13123059.
Mucin-5AC (MUC5AC) is a heavily glycosylated gel-forming secreted mucin with a reliable prognostic value when detected in multiple malignancies. It is highly prevalent (70%) in PDA and is nonexistent in normal pancreatic tissues. Retrospective studies on PDA tumor tissue (detected by immunohistochemistry or IHC)) have investigated the prognostic value of MUC5AC expression but were equivocal. Some studies associated it with poor outcomes (survival or pathological features such as lymph node disease, vascular/neural invasion in resected tumors), while others have concluded that it is a good prognostic marker. The examination of expression level threshold (5%, 10%, or 25%) and the detected region (apical vs. cytoplasmic) were variable among the studies. The maturation stage and glycoform of MUC5AC detected also differed with the Monoclonal antibody (Mab) employed for IHC. CLH2 detects less mature/less glycosylated versions while 45M1 or 21-1 detect mature/more glycosylated forms. Interestingly, aberrantly glycosylated variants of MUC5AC were detected using lectin assays (Wheat Germ Agglutinin-MUC5AC), and Mabs such as NPC-1C and PAM4 have are more specific to malignant pancreatic tissues. NPC-1C and PAM4 antibody reactive epitopes on MUC5AC are immunogenic and could represent specific changes on the native MUC5AC glycoprotein linked to carcinogenesis. It was never studied to predict treatment response.
黏蛋白5AC（MUC5AC）是一种高度糖基化的、可形成凝胶的分泌型黏蛋白，在多种恶性肿瘤中检测到它时具有可靠的预后价值。它在胰腺癌（PDA）中高度普遍（70%），而在正常胰腺组织中不存在。对PDA肿瘤组织（通过免疫组织化学或IHC检测）的回顾性研究探讨了MUC5AC表达的预后价值，但结果并不明确。一些研究将其与不良预后（生存率或病理特征，如淋巴结疾病、切除肿瘤中的血管/神经侵犯）相关联，而另一些研究则得出结论，认为它是一个良好的预后标志物。研究之间在表达水平阈值（5%、10%或25%）和检测区域（顶端与细胞质）的检查方面存在差异。检测到的MUC5AC的成熟阶段和糖型也因用于IHC的单克隆抗体（Mab）而异。CLH2检测到的是成熟度较低/糖基化程度较低的版本，而45M1或21-1检测到的是成熟/糖基化程度较高的形式。有趣的是，使用凝集素测定法（麦胚凝集素-MUC5AC）检测到了MUC5AC的异常糖基化变体，并且诸如NPC-1C和PAM4等单克隆抗体对恶性胰腺组织更具特异性。MUC5AC上的NPC-1C和PAM4抗体反应表位具有免疫原性，可能代表与致癌作用相关的天然MUC5AC糖蛋白的特定变化。从未对其进行过预测治疗反应的研究。
Zotero 插件