Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

Leonora SF Boogerd,1 Maxime JM van der Valk,1 Martin C Boonstra,1 Hendrica AJM Prevoo,1 Denise E Hilling,1 Cornelis JH van de Velde,1 Cornelis FM Sier,1 Arantza Fariña Sarasqueta,2 Alexander L Vahrmeijer1 1Department of Surgery, 2Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands 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