Duxbury Mark S, Matros Evan, Clancy Thomas, Bailey Gerald, Doff Michael, Zinner Michael J, Ashley Stanley W, Maitra Anirban, Redston Mark, Whang Edward E
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ann Surg. 2005 Mar;241(3):491-6. doi: 10.1097/01.sla.0000154455.86404.e9.
The purpose of this study was to test the hypothesis that CEACAM6 expression is an indicator of adverse pathologic features and clinical outcome in pancreatic adenocarcinoma.
Previously, we have demonstrated carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) to be an oncoprotein that plays an important role in the biology of pancreatic adenocarcinoma. Suppression of CEACAM6 expression reduces tumorigenesis and metastasis in vivo.
A tissue microarray was constructed using tumor specimens obtained from 89 consecutive patients who had undergone pancreatic resection for pancreatic adenocarcinoma with curative intent. A second microarray containing 54 pancreatic intraepithelial neoplasia (PanIN) lesions was constructed using tissues from a separate cohort of 44 patients. Both arrays were immunostained using a specific anti-CEACAM6 monoclonal antibody. Tumoral CEACAM6 expression was dichotomized into negative and positive immunoreactivity groups. The log-rank test was used to evaluate univariate associations of CEACAM6 expression with prognosis. Survival curves were derived using the Kaplan-Meier method.
Tumoral CEACAM6 expression was detected in 82 (92%) pancreatic adenocarcinoma specimens. CEACAM6 expression was more prevalent in high-grade than in low-grade PanIN lesions (P = 0.0002). Negative tumoral CEACAM6 expression was associated with absence of lymph node metastases (P = 0.012), lower disease stage (P = 0.008), and longer postoperative survival (P = 0.047).
CEACAM6 is a novel biomarker for pancreatic adenocarcinoma. CEACAM6 warrants further evaluation as both a prognostic factor and a therapeutic target in pancreatic cancer.
本研究旨在验证以下假设，即癌胚抗原相关细胞黏附分子6（CEACAM6）的表达是胰腺腺癌不良病理特征和临床结局的一个指标。
此前，我们已证明癌胚抗原相关细胞黏附分子6（CEACAM6）是一种癌蛋白，在胰腺腺癌生物学中发挥重要作用。抑制CEACAM6的表达可减少体内肿瘤发生和转移。
使用从89例连续接受根治性胰腺切除术的胰腺腺癌患者获得的肿瘤标本构建组织芯片。使用来自另一组44例患者的组织构建包含54个胰腺上皮内瘤变（PanIN）病变的第二个芯片。两个芯片均使用特异性抗CEACAM6单克隆抗体进行免疫染色。肿瘤CEACAM6表达分为阴性和阳性免疫反应性组。采用对数秩检验评估CEACAM6表达与预后的单变量关联。使用Kaplan-Meier方法得出生存曲线。
在82例（92%）胰腺腺癌标本中检测到肿瘤CEACAM6表达。CEACAM6表达在高级别PanIN病变中比在低级别病变中更常见（P = 0.0002）。肿瘤CEACAM6阴性表达与无淋巴结转移（P = 0.012）、较低疾病分期（P = 0.008）和较长术后生存期（P = 0.047）相关。
CEACAM6是胰腺腺癌的一种新型生物标志物。CEACAM6作为胰腺癌的预后因素和治疗靶点值得进一步评估。
