Uehara H, Nakaizumi A, Tatsuta M, Baba M, Takenaka A, Uedo N, Sakai N, Yano H, Iishi H, Ohigashi H, Ishikawa O, Okada S, Kakizoe T
Department of Gastroenterology, Osaka Medical Center for Cancer and Cardiovascular Disease, Higashinari, Japan.
Am J Gastroenterol. 1999 Sep;94(9):2513-8. doi: 10.1111/j.1572-0241.1999.01386.x.
Telomerase activity is reported to be specific and very frequent in human malignancy. K-ras mutations are also very frequently detected in pancreatic cancer, but their specificity for pancreatic cancer is controversial. We examined the telomerase activity and K-ras mutations in pancreatic juice from patients with pancreatic disease.
Pancreatic juice was obtained endoscopically at endoscopic retrograde pancreatography from 10 patients with pancreatic cancer, three with chronic pancreatitis, and three with a normal pancreas. The telomerase activity in pancreatic juice was assayed by telomeric repeat amplification protocol. K-ras mutations in exon 1 codon 12 were examined by the two-step polymerase chain reaction combined with restriction enzyme digestion, followed by single-strand conformation polymorphism analysis and direct sequencing.
Telomerase activity of >5.0 was detected in eight of 10 (80%) subjects with pancreatic cancer, but in none with chronic pancreatitis or normal pancreas. K-ras mutations were detected not only in eight of 10 (80%) subjects with pancreatic cancer but also in two of three with chronic pancreatitis and in one of three with a normal pancreas.
It was shown that the detection of telomerase activity in pancreatic juice is a more useful diagnostic tool for pancreatic cancer than that of K-ras mutations.
据报道，端粒酶活性在人类恶性肿瘤中具有特异性且非常常见。K-ras突变在胰腺癌中也经常被检测到，但其对胰腺癌的特异性存在争议。我们检测了胰腺疾病患者胰液中的端粒酶活性和K-ras突变。
通过内镜逆行胰胆管造影术从10例胰腺癌患者、3例慢性胰腺炎患者和3例胰腺正常的患者中获取胰液。采用端粒重复序列扩增法检测胰液中的端粒酶活性。通过两步聚合酶链反应结合限制性内切酶消化，随后进行单链构象多态性分析和直接测序，检测第1外显子第12密码子的K-ras突变。
10例胰腺癌患者中有8例（80%）检测到端粒酶活性>5.0，但慢性胰腺炎患者和胰腺正常者均未检测到。K-ras突变不仅在10例胰腺癌患者中的8例（80%）中被检测到，而且在3例慢性胰腺炎患者中的2例以及3例胰腺正常者中的1例中也被检测到。
结果表明，检测胰液中的端粒酶活性对胰腺癌的诊断比检测K-ras突变更有用。
