Colorectal polyps: Targets for fluorescence‐guided endoscopy to detect high‐grade dysplasia and T1 colorectal cancer

United European Gastroenterology Journal, vol. 11, pp. 282–292

Abstract

BACKGROUND: Differentiating high-grade dysplasia (HGD) and T1 colorectal cancer (T1CRC) from low-grade dysplasia (LGD) in colorectal polyps can be challenging. Incorrect recognition of HGD or T1CRC foci can lead to a need for additional treatment after local resection, which might not have been necessary if it was recognized correctly. Tumor-targeted fluorescence-guided endoscopy might help to improve recognition. OBJECTIVE: Selecting the most suitable HGD and T1CRC-specific imaging target from a panel of well-established biomarkers: carcinoembryonic antigen (CEA), c-mesenchymal-epithelial transition factor (c-MET), epithelial cell adhesion molecule (EpCAM), folate receptor alpha (FRα), and integrin alpha-v beta-6 (αvβ6). METHODS: En bloc resection specimens of colorectal polyps harboring HGD or T1CRC were selected. Immunohistochemistry on paraffin sections was used to determine the biomarker expression in normal epithelium, LGD, HGD, and T1CRC (scores of 0-12). The differential expression in HGD-T1CRC components compared to surrounding LGD and normal components was assessed, just as the sensitivity and specificity of each marker. RESULTS: 60 specimens were included (21 HGD, 39 T1CRC). Positive expression (score >1) of HGD-T1CRC components was found in 73.3%, 78.3%, and 100% of cases for CEA, c-MET, and EpCAM, respectively, and in <40% for FRα and αvβ6. Negative expression (score 0-1) of the LGD component occurred more frequently for CEA (66.1%) than c-MET (31.6%) and EpCAM (0%). The differential expression in the HGD-T1CRC component compared to the surrounding LGD component was found for CEA in 66.7%, for c-MET in 43.1%, for EpCAM in 17.2%, for FRα in 22.4%, and for αvβ6 in 15.5% of the cases. Moreover, CEA showed the highest combined sensitivity (65.0%) and specificity (75.0%) for the detection of an HGD-T1CRC component in colorectal polyps. CONCLUSION: Of the tested targets, CEA appears the most suitable to specifically detect HGD and T1 cancer foci in colorectal polyps. An in vivo study using tumor-targeted fluorescence-guided endoscopy should confirm these findings.

Authors 14

1. Nik Dekkers corresponding Aachen Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands Department of Gastroenterology and Hepatology

   Leiden University Medical Center

   Affiliation as printed

   Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands

   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

2. Elham Zonoobi Aachen Department of Surgery Leiden University Medical Center Leiden the Netherlands Department of Surgery, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Surgery Leiden University Medical Center Leiden The Netherlands

   Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

3. Hao Dang Aachen Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands Department of Gastroenterology and Hepatology

   Leiden University Medical Center

   Affiliation as printed

   Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands

   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

4. Mats I. Warmerdam Aachen Department of Surgery Leiden University Medical Center Leiden the Netherlands Department of Surgery, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Surgery Leiden University Medical Center Leiden The Netherlands

   Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

5. Stijn Crobach Aachen Department of Pathology Leiden University Medical Center Leiden The Netherlands Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology Leiden University Medical Center Leiden The Netherlands

   Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

6. Alexandra M. J. Langers Aachen Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands Department of Gastroenterology and Hepatology

   Leiden University Medical Center

   Affiliation as printed

   Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands

   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

7. Jolein van der Kraan Aachen Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands Department of Gastroenterology and Hepatology

   Leiden University Medical Center

   Affiliation as printed

   Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands

   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

8. Denise E. Hilling Aachen Department of Surgery Leiden University Medical Center Leiden the Netherlands Department of Surgery, Leiden University Medical Center

   Leiden University Medical Center · Erasmus MC

   Affiliation as printed

   Department of Surgery Leiden University Medical Center Leiden The Netherlands

   Department of Surgical Oncology and Gastrointestinal Surgery University Medical Center Rotterdam Rotterdam The Netherlands

   Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

   Department of Surgical Oncology and Gastrointestinal Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands

9. Koen C.M.J. Peeters Aachen Department of Surgery Leiden University Medical Center Leiden the Netherlands Department of Surgery, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Surgery Leiden University Medical Center Leiden The Netherlands

   Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

10. Fabian A. Holman Aachen Department of Surgery Leiden University Medical Center Leiden the Netherlands Department of Surgery, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Surgery Leiden University Medical Center Leiden The Netherlands

    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

11. Alexander L. Vahrmeijer Aachen Department of Surgery Leiden University Medical Center Leiden the Netherlands Department of Surgery, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Surgery Leiden University Medical Center Leiden The Netherlands

    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

12. Cornelis F.M. Sier Aachen Department of Surgery Leiden University Medical Center Leiden the Netherlands Department of Surgery, Leiden University Medical Center

    Leiden University Medical Center · Percuros (Netherlands)

    Affiliation as printed

    Department of Surgery Leiden University Medical Center Leiden The Netherlands

    Percuros BV Leiden The Netherlands

    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

    Percuros BV, Leiden, The Netherlands

13. James C.H. Hardwick Aachen Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands Department of Gastroenterology and Hepatology

    Leiden University Medical Center

    Affiliation as printed

    Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands

    Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

14. Jurjen J. Boonstra Aachen Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands Department of Gastroenterology and Hepatology

    Leiden University Medical Center

    Affiliation as printed

    Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands

    Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands