Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy.

PURPOSE: Intraoperative identification of rectal cancer (RC) can be challenging, especially because of fibrosis after treatment with preoperative chemo- and radiotherapy (CRT). Tumor-targeted fluorescence imaging can enhance the contrast between tumor and normal tissue during surgery. Promising targets for RC imaging are carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM) and the tyrosine-kinase receptor Met (c-Met). The effect of CRT on their expression determines their applicability for imaging. Therefore, we investigated whether CRT modifies expression patterns in tumors, lymph node (LN) metastases and adjacent normal rectal tissues. PATIENTS AND METHODS: Preoperative biopsies, primary tumor specimens and metastatic LNs were collected from 38 RC patients who did not receive CRT (cohort 1) and 34 patients who did (cohort 2). CEA, EpCAM and c-Met expression was determined using immunohistochemical staining and was semiquantified by a total immunostaining score (TIS), consisting of the percentage and intensity of stained tumor cells (0-12). RESULTS: In both cohorts CEA, EpCAM and c-Met were significantly highly expressed in >60% of tumor tissues compared with adjacent normal epithelium (T/N ratio, P<0.01). EpCAM showed the most homogenous expression in tumors, whereas CEA showed the highest T/N ratio. Most importantly, CEA and EpCAM expression did not significantly change in normal or neoplastic RC tissue after CRT, whereas levels of c-Met changed (P=0.02). Tissues of eight patients with a pathological complete response after CRT showed expression of all biomarkers with TIS close to normal epithelium. CONCLUSION: Histological evaluation shows that CEA, EpCAM and c-Met are suitable targets for RC imaging, because all three are significantly enhanced in cancer tissue from primary tumors or LN metastases compared with normal adjacent tissue. Furthermore, the expression of CEA and EpCAM is not significantly changed after CRT. These data underscore the applicability of c-Met and especially, CEA and EpCAM as targets for image-guided RC surgery, both before and after CRT.

In Search for Optimal Targets for Intraoperative Fluorescence Imaging of Peritoneal Metastasis From Colorectal Cancer.

Peritoneal metastasis (PM) occurs in about 10% of patients with colorectal cancer (CRC). Fluorescence imaging can enhance contrast between cancerous and benign tissue, enabling the surgeon to clearly visualize PM during cytoreductive surgery. This study assessed the suitability of different biomarkers as potential targets for tumor-targeted imaging of PM of CRC. Tissue samples from primary tumor and PM from patients with CRC were obtained from the pathology archives and immunohistochemical stainings were performed. Overexpression of the epithelial cell adhesion molecule (EpCAM) and carcinoembryonic antigen (CEA) was seen in 100% of PM samples and the expression was strong in >70% of samples. Tyrosine-kinase Met (C-Met) and folate receptor α overexpression was seen in 20% of PM samples. For successful application of tumor-targeted intraoperative fluorescence imaging of PM, biomarkers need to be identified. We demonstrated that both EpCAM and CEA are suitable targets for fluorescence imaging of PM in patients with CRC.

Prognostic Impact of Urokinase Plasminogen Activator Receptor Expression in Pancreatic Cancer: Malignant Versus Stromal Cells.

The urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for various malignancies. The aim of this study is to assess the prognostic value of uPAR expression in neoplastic and stromal cells of patients with pancreatic adenocarcinoma. Urokinase plasminogen activator receptor expression was determined by immunohistochemistry in 122 pancreatic ductal adenocarcinomas. Kaplan-Meier and Cox regression analyses were used to determine the association with survival. Respectively 66%, 82% and 62% of patients with pancreatic cancer expressed uPAR in neoplastic cells, stromal, and in both combined. Multivariate analysis showed a significant inverse association between uPAR expression in both neoplastic and stromal cells and overall survival. The prognostic impact of uPAR in stromal cells is substantial, but not as pronounced as that of uPAR expression in neoplastic cells. This study suggests a role for uPAR as a biomarker to single out higher risk subgroups of patients with pancreatic cancer.