Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

Area of Science:

• Oncology
• Surgical Imaging
• Biomarker Expression

Background:

• Intraoperative identification of rectal cancer (RC) is challenging, particularly after neoadjuvant chemo-radiotherapy (CRT) due to fibrosis.
• Tumor-targeted fluorescence imaging offers potential for enhanced contrast between cancerous and normal tissues during surgery.
• Carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), and c-Met are promising targets for RC imaging.

Purpose of the Study:

• To investigate the impact of CRT on the expression patterns of CEA, EpCAM, and c-Met in RC tumors, lymph node (LN) metastases, and adjacent normal rectal tissues.
• To determine the suitability of these biomarkers for image-guided RC surgery, both before and after CRT.

Main Methods:

• Collected preoperative biopsies, primary tumor specimens, and metastatic LNs from 72 RC patients (38 without CRT, 34 with CRT).
• Assessed CEA, EpCAM, and c-Met expression using immunohistochemical staining.
• Quantified expression via a total immunostaining score (TIS) based on staining percentage and intensity.

Main Results:

• CEA, EpCAM, and c-Met were significantly overexpressed in tumor tissues compared to adjacent normal epithelium across both patient cohorts (T/N ratio, P<0.01).
• EpCAM exhibited the most homogeneous expression in tumors, while CEA showed the highest tumor-to-normal ratio.
• CEA and EpCAM expression remained largely unchanged after CRT, whereas c-Met levels were significantly altered (P=0.02). Pathological complete response tissues showed biomarker expression similar to normal tissue.

Conclusions:

• CEA, EpCAM, and c-Met are suitable targets for RC imaging due to significant enhancement in cancer tissue (primary tumors and LNs) versus normal tissue.
• CEA and EpCAM expression stability post-CRT supports their use in image-guided surgery irrespective of treatment status.
• These findings highlight the applicability of CEA and EpCAM, and to a lesser extent c-Met, as targets for image-guided RC surgery before and after CRT.