Serum Tumor Markers and Molecular Biological Diagnosis in Pancreatic Cancer-猫眼课题宝

DOI：

10.1097/00006676-200404000-00009

发表时间：

2004-04

期刊：

Pancreas

影响因子：

2.9

通讯作者：

中科院分区：

医学4区

文献类型：

--

作者：

N. Sawabu;Hiroyuki Watanabe;Y. Yamaguchi;K. Ohtsubo;Y. Motoo

摘要：近年来，对胰腺导管癌遗传异常的研究，引起了对血清和胰液中肿瘤标志物和遗传标志物的研究。血清1型糖链抗原（CA 19 -9）在胰腺癌（PCa）患者中的阳性率接近80%，其中大多数为晚期，而在良性肝胆胰疾病中的假阳性率相对较高，约为20%~ 30%。虽然2型链碳水化合物抗原（如SLX）的流行率相对较低，但这些抗原的癌症特异性较高。然而，血清肿瘤标志物对PCa的早期诊断价值有限。在内镜下收集的PCa患者的PJ中，K-ras突变（KRM）在> 80%中可检测到，而在慢性胰腺炎（CP）患者的PJ中观察到20%-30%的KRM，反映了携带KRM的良性粘液细胞增生。因此，PJ中KRM的定性分析不适合于PCa的诊断。另一方面，使用可定量测定KRM的杂交保护试验，66%的PCa中KRM为阳性，而CP仅为40%，表明PJ中KRM的定性分析可能有助于PCa与CP的鉴别。在PCa患者的PJ中发现4%-50%的p53突变，但在CP患者的PJ中未检测到p53突变，表明p53突变对PCa的特异性非常高。此外，在PJ细胞学诊断为阴性的15例PCa患者中，有7例（47%）检测到p53突变。端粒酶（TE）活性或其催化亚基h-TERT在前列腺癌PJ中的阳性率>80%，而在前列腺癌PJ中的阳性率<20%。CP的PJ中TE活性来源于淋巴细胞。这些新的遗传和表观遗传标记物的开发和应用具有高特异性和敏感性的血清和PJ中的PCa将显着提高我们的诊断准确性。

Abstract: Recent studies on genetic abnormalities in pancreatic ductal cancer have led to the investigation of tumor markers and genetic markers in both serum and pancreatic juice (PJ). Serum type 1 chain carbohydrate antigens such as CA19-9 are positive in nearly 80% of patients with pancreatic cancer (PCa), of which most are in advanced stage, whereas false-positive rates are relatively high at 20%–30% in benign hepatobiliary and pancreatic diseases. Although the prevalence of type 2 chain carbohydrate antigens, such as SLX, is relatively low, cancer specificity of these antigens is high. However, serum tumor markers have limited diagnostic value for early detection of PCa. In PJ collected endoscopically from patients with PCa, K-ras mutations (KRM) are detectable in > 80%, whereas KRM are observed in 20%–30% of PJ from patients with chronic pancreatitis (CP), reflecting benign mucous cell hyperplasia harboring KRM. Thus, a qualitative analysis of KRM in PJ is unsuitable for diagnosis of PCa. On the other hand, using an hybridization protection assay that can quantitatively determine KRM, KRM were positive in 66% of PCa but only in 40% of CP cases, indicating that qualitative analysis of KRM in PJ may be useful for differentiating PCa from CP. p53 Mutations are found in 4%–50% in PJ from patients with PCa but are not detectable in PJ from CP, suggesting that the specificity of p53 mutations is very high for PCa. Furthermore, p53 mutations were detected in 7 of 15 (47%) patients with PCa in which the PJ cytologic diagnosis was negative. Telomerase (TE) activity or its catalytic subunit, h-TERT, was reportedly positive >80% in PJ from PCa but was detected in <20% of PJ from CP. TE activity in PJ from CP originates from lymphocytes. The development and application of these new genetic and epigenetic markers with high specificity and sensitivity for PCa in serum and PJ will significantly improve our diagnostic accuracy.