We explored the differential expression and diagnostic value of two significant Mucin 5AC (MUC5AC) glycoforms, less-glycosylated immature (IM) and heavily-glycosylated mature (MM), in neoplastic diseases (NpD), including pancreatic ductal adenocarcinoma (PDA) and neuroendocrine tumors (NET), and non-neoplastic (non-NpD) diseases. Commercially available tissue microarray (TMA) was constructed from 96 patients, including 38 primary PDA (PT), 5 metastatic lesions (ML), 11 NET, and the rest being non-NpD tissues. Immunohistochemistry for MUC5AC was performed using CHL2 and 45M1 clones for IM and MM isoforms, respectively. MUC5AC (both glycoforms) are not detected in non-NpD. In MUC5AC-positive neoplastic tissues, IM was localized to the cytoplasm (Cy) while MM was identified in apical (Ap) and extracellular (Ec) regions too. One ML positive (omentum) in the TMA expressed both. For PDA vs. non-PDA, the sensitivity (SN) was higher with MM ± IM (71%) than MM (47%) or IM (65%)-alone. The specificity (SP) was 100% with MM-alone, which dropped with the addition of IM (96%) or IM-alone (93%). For NpD vs. non-NpD, the SN (MM + IM-59%, IM-55%, MM-37%) was inferior, and SP was 100% for both glycoforms (MM ± IM). The combination of MUC5AC glycoforms has high SP and reasonable SN to diagnose PDA. They have the potential to be a reliable diagnostic marker and should be investigated further in more extensive studies.
本研究探讨了两种重要的黏蛋白5AC（MUC5AC）糖型——低糖基化未成熟型（IM）与高糖基化成熟型（MM）——在肿瘤性疾病（包括胰腺导管腺癌（PDA）与神经内分泌肿瘤（NET））及非肿瘤性疾病中的差异表达及其诊断价值。通过商业组织芯片（TMA）对96例患者样本进行分析，包括38例原发性PDA、5例转移性病灶、11例NET及非肿瘤组织。采用CHL2与45M1克隆分别对MUC5AC的IM与MM亚型进行免疫组化检测。结果显示，非肿瘤组织中未检测到MUC5AC（两种糖型）。在MUC5AC阳性的肿瘤组织中，IM定位于细胞质，而MM同时出现在顶端区域及细胞外区域。TMA中一例转移性病灶（大网膜）同时表达两种糖型。在PDA与非PDA的鉴别诊断中，MM±IM联合检测的敏感性（71%）高于单独使用MM（47%）或IM（65%）；单独使用MM的特异性为100%，而联合IM或单独使用IM时特异性略有下降（分别为96%和93%）。在肿瘤性疾病与非肿瘤性疾病的鉴别中，两种糖型的敏感性均较低（MM+IM为59%，IM为55%，MM为37%），但特异性均达100%。研究表明，联合检测MUC5AC糖型对诊断PDA具有高特异性与合理敏感性，有望成为可靠的诊断标志物，值得在更广泛的研究中进一步验证。
肿瘤(癌症)患者之家