Evaluation of the anti-Thomsen-Friedenreich antibodies Nemod-TF1 and Nemod-TF2 as prognostic markers in breast cancer

Breast Cancer Res Treat. 2020 Feb;179(3):643-652. doi: 10.1007/s10549-019-05503-6. Epub 2019 Dec 11.

Abstract

Purpose: The TF (Thomsen-Friedenreich, CD176, GalĪ²1-3GalNAc) carbohydrate moiety is known as a specific oncofetal carbohydrate epitope present in fetal and neoplastic tissue as well as in stem cells. TF was demonstrated to mediate tumor-promoting features and to be highly immunogenic. The current study aimed to evaluate whether presence of the TF antigen is associated with clinico-pathological parameters and prognosis of early breast cancer (BC).

Methods: Primary BC tissue (n = 226) was stained for TF using two monoclonal anti-TF antibodies (Nemod-TF1, Nemod-TF2). Staining results were correlated to clinical data including survival.

Results: Nemod-TF1 staining was positively correlated to lymph node metastasis (p = 0.03) and the presence of tumor-associated MUC1 (TA-MUC1; p = 0.003). Further, the presence of the Nemod-TF1 epitope predicted worse prognosis in TA-MUC1 positive (overall survival: p = 0.026) as well as in triple negative (overall survival: p = 0.002; distant metastasis-free survival: p = 0.012) BC.

Conclusions: The data presented here further support a role of TF in BC tumor biology. Whether anti-TF directed treatment approaches may gain clinical relevance in those cases determined as triple negative or TA-MUC1 positive remains to be determined.

Keywords: Breast cancer; CD176; Nemod-TF1/2; Prognosis.

MeSH terms

  • Antibodies / immunology*
  • Antibodies, Monoclonal, Humanized / metabolism
  • Antigens, Neoplasm / immunology
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Biomarkers, Tumor / immunology
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / pathology
  • Middle Aged
  • Mucin-1 / metabolism*
  • Prognosis
  • Triple Negative Breast Neoplasms / diagnosis*
  • Triple Negative Breast Neoplasms / mortality*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antibodies
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate
  • Biomarkers, Tumor
  • MUC1 protein, human
  • Mucin-1
  • PankoMab-GEX
  • Thomsen-Friedenreich antigen
  • Thomsen-Friedenreich antibodies