TdT expression in germ cell tumours: a possible immunohistochemical cross-reaction and diagnostic pitfall

J Clin Pathol. 2019 Aug;72(8):536-541. doi: 10.1136/jclinpath-2019-205713. Epub 2019 May 4.

Abstract

Aims: Very recent papers proposed a possible role for the expression of terminal deoxynucleotidyl transferase (TdT) in the tumourigenesis of gonadal and extragonadal germ cell-derived tumours (GCTs). Our multicentric study evaluated the magnitude of the immunoreactivity for TdT in GCTs, encompassing seminoma, dysgerminoma, mature teratoma and mixed GCTs.

Methods and results: The histological series was stained with both monoclonal and polyclonal antibodies, yielding a positivity of 80% of cases with well-defined nuclear reactivity. A significant difference in staining intensity between monoclonal and polyclonal antibodies was observed (p=0.005). However, exploiting western blot and more innovative proteomic approaches, no clear-cut evidence of the TdT protein was observed in the neoplastic tissues of the series.

Conclusions: Alternatively to the pathogenetic link between TdT expression and GCTs tumourigenesis, we hypothesised the occurrence of a spurious immunohistochemical nuclear cross-reaction, a well-known phenomenon with important implications and a possible source of diagnostic pitfalls in routine practice for pathologists.

Keywords: differential diagnosis; genital system; germinal cell tumor; haematopoietic; seminoma; tdt; terminal deoxynucleotidyl transferase.

Publication types

  • Multicenter Study

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibody Specificity*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / immunology
  • Cross Reactions
  • DNA Nucleotidylexotransferase / analysis*
  • DNA Nucleotidylexotransferase / immunology
  • Female
  • Humans
  • Immunohistochemistry*
  • Italy
  • Male
  • Mediastinal Neoplasms / enzymology*
  • Mediastinal Neoplasms / immunology
  • Mediastinal Neoplasms / pathology
  • Neoplasms, Germ Cell and Embryonal / enzymology*
  • Neoplasms, Germ Cell and Embryonal / immunology
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Predictive Value of Tests
  • Reproducibility of Results
  • Testicular Neoplasms / enzymology*
  • Testicular Neoplasms / immunology
  • Testicular Neoplasms / pathology

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • DNA Nucleotidylexotransferase