Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

Abstract

PurposeIntraoperative 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 methodsPreoperative 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).ResultsIn 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.ConclusionHistological 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.

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

“…Another prerequisite is that the biomarker's expression on tumor cells is not significantly altered by preoperative radiotherapy since this is often used for MFS. For a variety of tumor types there are established suitable targets for molecular imaging, but for MFS specific immunohistochemical expression profiles have not yet been described [17][18][19][20] .…”

CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy

“…Previous research has shown that CEA and EpCAM expression is upregulated in rectal cancer cells compared with adjacent pre-existent rectal mucosa [ 20 , 34 ]. A previous study by our group has demonstrated that CEA and EpCAM are still overexpressed in patients with a partial or no response after neoadjuvant therapy [ 20 , 34 , 35 ]. In that study, CEA and EpCAM expression after neoadjuvant therapy was high (TIS > 6) in respectively 93% and 100% of the partial- and nonresponders [ 35 ].…”

“…A previous study by our group has demonstrated that CEA and EpCAM are still overexpressed in patients with a partial or no response after neoadjuvant therapy [ 20 , 34 , 35 ]. In that study, CEA and EpCAM expression after neoadjuvant therapy was high (TIS > 6) in respectively 93% and 100% of the partial- and nonresponders [ 35 ]. The current study demonstrates that CEA and EpCAM have an absent or low expression (TIS < 6) in the tumor bed of nearly all patients with a pCR after neoadjuvant therapy.…”

“…Previous immunohistochemical data demonstrated that CEA and EpCAM expression in rectal cancer cells and adjacent pre-existent mucosa does not change after neoadjuvant therapy. It showed that these proteins are still overexpressed in patients with a partial or no response after neoadjuvant therapy [ 35 ]. These findings suggest CEA and EpCAM are suitable targets for accurate response evaluation after neoadjuvant therapy using fluorescence endoscopy.…”

Fluorescent‐guided surgery for sentinel lymph node detection in gastric cancer and carcinoembryonic antigen targeted fluorescent‐guided surgery in colorectal and pancreatic cancer

“…The combination of a good level of contrast between healthy and cancer tissue and high antigenic density makes CEA an excellent candidate for fluorescent‐guided surgery in CRC. Furthermore, CEA expression does not seem to alter after neoadjuvant therapy …”