Walter Kim, Hong Seung-Mo, Nyhan Sinead, Canto Marcia, Fedarko Neal, Klein Alison, Griffith Margaret, Omura Noriyuki, Medghalchi Susan, Kuhajda Frank, Goggins Michael
Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2380-5. doi: 10.1158/1055-9965.EPI-09-0144. Epub 2009 Sep 1.
Markers of early pancreatic cancer and its precursors are needed to improve the uniformly poor prognosis of this disease. Fatty acid synthase (FAS) catalyzes the synthesis of long-chain fatty acids and is overexpressed in most human solid tumors. We therefore evaluated serum FAS as a marker of pancreatic adenocarcinoma. FAS expression patterns in primary pancreatic adenocarcinomas, intraductal papillary mucinous neoplasms (IPMN), and chronic pancreatitis tissues were analyzed by immunohistochemistry. Serum FAS levels were determined by ELISA in 102 patients with pancreatic adenocarcinomas, in 42 patients with IPMNs, in 27 patients with chronic pancreatitis, and in 39 healthy control subjects. FAS protein was overexpressed in the ductal epithelium of 343 of 399 primary pancreatic adenocarcinomas (86.0%) and 28 of 30 IPMNs (93.3%), and in the islet and ductal cells in 3 of 54 chronic pancreatitis tissues (5.6%), whereas normal ductal epithelium lacked FAS expression. Serum FAS levels were significantly higher in patients with pancreatic ductal adenocarcinoma (first quartile median, 22.0; 4.5 ng/mL), in patients with IPMNs (20.7; 9.4 ng/mL), and in patients with chronic pancreatitis (31.1; 11.9 ng/mL) than in healthy controls (0; 0 ng/mL). FAS levels declined postoperatively in 8 of 9 patients with pancreatic adenocarcinoma and elevations of their preoperative serum FAS. In conclusion, serum FAS levels are elevated in patients with pancreatic cancer and IPMNs and are associated with neoplastic overexpression of FAS.
需要早期胰腺癌及其癌前病变的标志物来改善这种疾病普遍较差的预后。脂肪酸合酶(FAS)催化长链脂肪酸的合成,在大多数人类实体瘤中过表达。因此,我们评估了血清FAS作为胰腺腺癌的标志物。通过免疫组织化学分析原发性胰腺腺癌、导管内乳头状黏液性肿瘤(IPMN)和慢性胰腺炎组织中的FAS表达模式。采用酶联免疫吸附测定(ELISA)法测定了102例胰腺腺癌患者、42例IPMN患者、27例慢性胰腺炎患者和39名健康对照者的血清FAS水平。FAS蛋白在399例原发性胰腺腺癌中的343例(86.0%)和30例IPMN中的28例(93.3%)的导管上皮中过表达,在54例慢性胰腺炎组织中的3例(5.6%)的胰岛和导管细胞中过表达,而正常导管上皮缺乏FAS表达。胰腺导管腺癌患者(第一四分位数中位数,22.0;四分位距4.5 ng/mL)、IPMN患者(20.7;9.4 ng/mL)和慢性胰腺炎患者(31.1;11.9 ng/mL)的血清FAS水平显著高于健康对照者(0;0 ng/mL)。9例胰腺腺癌患者中有8例术后FAS水平下降,且术前血清FAS升高。总之,胰腺癌和IPMN患者的血清FAS水平升高,且与FAS的肿瘤性过表达相关。