肿瘤标志物(Tumor Marker)是证明肿瘤存在于人体内的生物化学类物质。它们在正常组织内含量很低。而在胚胎组织或在肿瘤组织中的含量明显高于在正常组织里的含量，不同肿瘤标志物的较高水平的存在或量变可以提示肿瘤的组织发生、分类、预后和疗效判定。 肿瘤标志物可以分为两类：1)肿瘤组织本身产生的，包括分化抗原、胚胎抗原(AFP,CEA)、同工酶(NSE)、激素(HCG)、组织特异性抗原(PSA,free PSA)、粘蛋白、糖蛋白、糖脂(CA125)、癌基因及其产物、多胺类等。2)肿瘤与宿主相互作用后产生的，包括血清铁蛋白、免疫复合物等。 80年代，杂交瘤技术获得了能识别肿瘤特异性大分子糖蛋白抗原(carbohydrate antigen, CA)[2]，并研制了单克隆抗体识别系统。CA是肿瘤细胞的相关抗原。常用的CA系列有：CA 125（卵巢癌相关抗原）；CA 19-9（胰腺、肠癌相关抗原）；CA 15-3（乳腺癌相关抗原）。 CA19-9是糖抗原的一种，许多研究已经证明了CA19-9表达增高多提示有胰腺炎、肝硬化、糖尿病、消化道肿瘤的可能。糖类抗原19-9升高见于：1.大部分胰腺癌患者血清CA19-9水平明显增高[3~10]；2.胆系癌[11~17]、胃癌、卵巢癌、结直肠癌和肝癌的CA 19-9水平也会升高；3.低浓度增高、一过性增高可见于慢性胰腺炎、胆管癌和胆石症[18,19]、肝硬化、肾功能不全、糖尿病等。 在CA19-9表达上调众多问题中，值得关注的一个问题是因为良性胆道病变导致的黄疸，CA19-9的表达也升高，有人提出这种重叠损害了CA19-9在评价胆管癌和胰腺癌的应用[5，9，10，20~23]。美国临床肿瘤协会（American Society of Clinical Oncology ）目前并没有主张其在胰腺癌筛查，可切除评价或疗效判定应用[24]。
如上所述，CA19-9 经常会在胰胆管肿瘤时表达都会升高，但对于良性胆道梗阻导致的黄疸的病人和其他非肝胆胰疾病人其表达也会升高。是否CA19-9水平能够精确鉴别良、恶性胰胆管疾病。Morris-Stiff等人[1]对经过病理证实的肝胆胰病变进行了分组研究。
他们的研究CA19-9水平良性比恶性病变显著降低。胰腺癌也可以鉴别胆管癌/十二癌，不可切除的胰腺癌也明显比可切除性癌更高。CA19-9敏感性，特异性，阳性预测值(positive predictive value PPV)，阴性预测值(negative predictive value NPV)分别是84.9%, 69.7%, 67.7% 和 86.1%。CA19-9，ROC分析提供曲线下面积0.871 (0.820-0.922)，良恶性鉴别诊断的理想的水平是70.5 U/ml。根据这一切割点（cut-off）敏感性82.1%，特异性, PPV 和 NPV 改善为 85.9%, 81.3%和86.5%。当联合标准放射学(US/CT/MRCP) 进行决策分析时，结果改善到97.2%, 88.7%, 86.6%和97.7%。对于良性病变，CA19-9直接与胆红素升高有关。而恶性病变的升高独立于胆红素的升高。 他们得出结论，当用理想切割点联合常规影像学检查时，CA19-9对于鉴别胰胆疾病是有用的，鉴别诊断显著的改善，这里强调了多种方法的联合应用。 1. Morris-Stiff G, Teli M, Jardine N, Puntis MC. CA19-9 antigen levels can distinguish between benign and malignant pancreaticobiliary disease.Hepatobiliary Pancreat Dis Int 2009; 8: 620-626 2. Del Villano BC, Brennan S, Brock P, Bucher C, Liu V, McClure M, et al. Radioimmunometric assay for a monoclonal antibody-defined tumor marker, CA 19-9. Clin Chem 1983;29:549-552. 3. Del Villano BC, Brennan S, Brock P, Bucher C, Liu V, McClure M, et al. Radioimmunometric assay for a monoclonal antibody-defined tumor marker, CA 19-9. Clin Chem 1983;29:549-552 4. Magnani JL, Steplewski Z, Koprowski H, Ginsburg V. Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Res 1983;43:5489-5492. 5. Del Favero G, Fabris C, Plebani M, Panucci A, Piccoli A, Perobelli L, et al. CA 19-9 and carcinoembryonic antigen in pancreatic cancer diagnosis. Cancer 1986;57:1576-1579. 6. Haglund C. Tumour marker antigen CA125 in pancreatic cancer: a comparison with CA19-9 and CEA. Br J Cancer 1986;54:897-901. 7. Steinberg WM, Gelfand R, Anderson KK, Glenn J, Kurtzman SH, Sindelar WF, et al. Comparison of the sensitivity and specificity of the CA19-9 and carcinoembryonic antigen assays in detecting cancer of the pancreas. Gastroenterology 1986;90:343-349. 8. Frebourg T, Bercoff E, Manchon N, Senant J, Basuyau JP, Breton P, et al. The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer. A prospective study of 866 patients. Cancer 1988;62:2287-2290. 9. Paganuzzi M, Onetto M, Marroni P, Barone D, Conio M, Aste H, et al. CA 19-9 and CA 50 in benign and malignant pancreatic and biliary diseases. Cancer 1988;61:2100-2108 10. Ritts RE Jr, Nagorney DM, Jacobsen DJ, Talbot RW, Zurawski VR Jr. Comparison of preoperative serum CA19-9 levels with results of diagnostic imaging modalities in patients undergoing laparotomy for suspected pancreatic or gallbladder disease. Pancreas 1994;9:707-716 11. Ker CG, Chen JS, Lee KT, Sheen PC, Wu CC. Assessment of serum and bile levels of CA19-9 and CA125 in cholangitis and bile duct carcinoma. J Gastroenterol Hepatol 1991;6:505-508 12. Nichols JC, Gores GJ, LaRusso NF, Wiesner RH, Nagorney DM, Ritts RE Jr. Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis. Mayo Clin Proc 1993;68:874-879. 13. Ramage JK, Donaghy A, Farrant JM, Iorns R, Williams R. Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastroenterology 1995;108:865-869 14. Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol 2000;95:204-207 15. Qin XL, Wang ZR, Shi JS, Lu M, Wang L, He QR. Utility of serum CA19-9 in diagnosis of cholangiocarcinoma: in comparison with CEA. World J Gastroenterol 2004;10:427- 432 16.John AR, Haghighi KS, Taniere P, Esmat ME, Tan YM, Bramhall SR. Is a raised CA 19-9 level diagnostic for a cholangiocarcinoma in patients with no history of sclerosing cholangitis? Dig Surg 2006;23:319-324. 17. Li YG, Zhang N. Clinical significance of serum tumour M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma. Dig Liver Dis 2009;41:605-608 18. Ong SL, Sachdeva A, Garcea G, Gravante G, Metcalfe MS, Lloyd DM, Berry DP, Dennison AR. Elevation of carbohydrate antigen 19-9 in benign hepatobiliary conditions and its correlation with serum bilirubin concentration. Dig Dis Sci 2008;53:3213-3217. 19. Sheen-Chen SM, Sun CK, Liu YW, Eng HL, Ko SF, Kuo CH. Extremely elevated CA19-9 in acute cholangitis. Dig Dis Sci 2007;52:3140-3142. 20. Benamouzig R, Buffet C, Fourre C, Ink O, Moati F, Etienne JP. Serum levels of carbohydrate antigenic determinant (CA 19.9) in obstructive jaundice. Dig Dis Sci 1989;34:1640-1642. 21. Basso D, Meggiato T, Fabris C, Plebani M, Fogar P, Panozzo MP, et al. Extra-hepatic cholestasis determines a reversible increase of glycoproteic tumour markers in benign and malignant diseases. Eur J Clin Invest 1992;22:800-804. 22. Collazos J, Genolla J, Ruibal A. CA 19-9 in non-neoplastic liver diseases. A clinical and laboratory study. Clin Chim Acta 1992;210:145-151. 23. Mery CM, Duarte-Rojo A, Paz-Pineda F, Gómez E, Robles-Díaz G. Does cholestasis change the clinical usefulness of CA 19-9 in pacreatobiliary cancer? Rev Invest Clin 2001; 53:511-517. 24. Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 2006;24:5313-5327. |