J Clin Med. 2018 Sep 5;7(9). pii: E256. doi: 10.3390/jcm7090256.

The Thomsen-Friedenreich Antigen: A Highly Sensitive and Specific Predictor of Microsatellite Instability in Gastric Cancer.

Mereiter S^1,², Polom K^3,⁴, Williams C⁵, Polonia A⁶, Guergova-Kuras M⁷, Karlsson NG⁸, Roviello F⁹, Magalhães A^10,¹¹, Reis CA^12,^13,^14,¹⁵.

Author information

1: I3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-465 Porto, Portugal. smereiter@ipatimup.pt.
2: IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal. smereiter@ipatimup.pt.
3: General Surgery and Surgical Oncology Department, University of Siena, 53100 Siena, Italy. surgoncolclub@gmail.com.
4: Department of Surgical Oncology, Medical University of Gdansk, 80-211 Gdańsk, Poland. surgoncolclub@gmail.com.
5: Ariana Pharmaceuticals, 75016 Paris, France. c.williams@arianapharma.com.
6: Department of Pathology, IPATIMUP Diagnostics, University of Porto, 4200-135 Porto, Portugal. apolonia@ipatimup.pt.
7: Ariana Pharmaceuticals, 75016 Paris, France. mariana.kuras@free.fr.
8: Medical Biochemistry, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden. niclas.karlsson@medkem.gu.se.
9: General Surgery and Surgical Oncology Department, University of Siena, 53100 Siena, Italy. franco.roviello@gmail.com.
10: I3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-465 Porto, Portugal. amagalhaes@ipatimup.pt.
11: IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal. amagalhaes@ipatimup.pt.
12: I3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-465 Porto, Portugal. celsor@ipatimup.pt.
13: IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal. celsor@ipatimup.pt.
14: Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal. celsor@ipatimup.pt.
15: Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal. celsor@ipatimup.pt.

Abstract

Microsatellite instability (MSI) is a distinct molecular subtype of gastric cancer. In recent years, the clinical consequences of MSI and the therapeutic opportunities to target this peculiar cancer subtype became evident. However, despite the importance of MSI for the stratification of patients, the time and resources required for diagnosis still present an obstacle. In an attempt to identify a new marker for MSI in gastric cancer, we evaluated the expression of five cancer-associated glycan epitopes in a cohort of 13 MSI and 17 microsatellite stable (MSS) cases. Our analysis revealed a highly significant (p < 0.001) association between the expression of the Thomsen-Friedenreich (TF) antigen and MSI status. Hence, we present here the identification of the first single marker for MSI in gastric cancer, excelling with a specificity of 94% (16/17), sensitivity of 69.2% (9/13), negative predictive value of 80% (16/20), and positive predictive value of 90% (9/10). The TF antigen, detected by simple antibody-based assays, is highly specific for carcinoma being undetectable in gastric healthy and premalignant epithelia. This finding lays the basis for new studies and holds promise in improving the rapid identification of MSI in the clinical setting.