The Prognostic Value of MUC16 (CA125) on the Cell Surface of Gastrointestinal Cancers
Mirte S Streppel, Audrey Vincent, Radha Mukherjee, Nathaniel Campbell, Shi-Hsun Chen, K Konstantopoulos, Michael Goggins, Isabelle Van Seuningen, Anirban Maitra, Elizabeth Montgomery. Johns Hopkins Medical Institutions, Baltimore; Université Lille-Nord de France, Lille Cedex, France
Background: Mucin core protein 16 (MUC16, CA125) is a cell surface glycoprotein that plays a role in promoting cancer cell growth and survival in ovarian cancer. We examined MUC16 expression in a large number of gastrointestinal carcinomas and precursor lesions to determine whether MUC16 up-regulation is correlated with patient outcome in gastrointestinal neoplasia.
Design: Tissue microarrays were constructed using surgical resection tissues from gastrointestinal adenocarcinoma patients. Tissue cores included: Pancreatic (115 normal, 11 precursors, 200 pancreatic ductal adenocarcinomas), Esophageal (86 normal, 104 precursors, 95 esophageal adenocarcinomas, 35 lymph node metastases); Gastric (176 normal, 43 precursors, 119 gastric adenocarcinomas, 62 lymph node metastases); Colorectal (34 normal, 17 precursors, 39 colorectal adenocarcinomas). Membranous MUC16 was scored and samples were categorized into four tiers: negative, focal, moderate, or diffuse staining. Six pancreatic and two esophageal adenocarcinoma cell lines were analyzed for MUC16 presence using Western Blot.
Results: MUC16 was detected in 81.5%, 69.9%, 41.2%, and 64.1% of the pancreatic ductal, esophageal, gastric, and colorectal adenocarcinomas, respectively. MUC16 was seen in a subset of non-invasive precursor lesions. Multivariate analysis indicated that moderate/diffuse MUC16 in pancreatic ductal adenocarcinomas is strongly associated with poor survival (P<0.001), independent of other prognosis predictors. A similar trend was observed for esophageal (P=0.160) and gastric adenocarcinomas (P=0.080). Focal MUC16 in colorectal adenocarcinomas was significantly correlated (P=0.044) with a better patient outcome, when compared to MUC16 negative cases. MUC16 was found in three pancreatic ductal and one esophageal adenocarcinoma cell lines.
Conclusions: We conclude that MUC16 expression occurs in the majority of the gastrointestinal adenocarcinomas and a subset of non-invasive precursor lesions. MUC16 expression is an independent predictor of poor outcome in pancreatic ductal adenocarcinomas, and potentially in gastric, and esophageal adenocarcinomas. As MUC16 expression appears to parallel aggressive tumor behavior, MUC16 may function as a prognostic marker and therapeutic target.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 66, Wednesday Morning