Expression of cytotoxic proteins by neoplastic T cells in mycosis fungoides increases with progression from plaque stage to tumor stage disease

Am J Pathol. 1999 Apr;154(4):1203-10. doi: 10.1016/S0002-9440(10)65372-2.


Granzyme B (GrB) and T-cell-restricted intracellular antigen (TIA-1) are cytotoxic proteins that are specifically expressed by cytotoxic CD4 or CD8 positive T cells and natural killer cells. Recent studies demonstrated frequent expression of GrB and TIA-1 by neoplastic cells in primary cutaneous CD30(+) large T-cell lymphomas and lymphomatoid papulosis but not in CD30(-) large T-cell lymphomas. In the present study, 74 biopsies from 54 patients with mycosis fungoides (MF) were investigated for the expression of GrB and TIA-1 using immunohistochemistry on paraffin sections. Staining of more than 10% of the neoplastic T cells for GrB or TIA-1 was considered positive. All but two follow-up biopsies had been obtained from patients without extracutaneous disease at the time of biopsy. Expression of TIA-1 and GrB was found in 33 (45%) and 14 (19%) of 74 MF biopsies, respectively. Comparison of biopsies from T3NoMo-stage MF (n = 27) and T2NoMo-stage MF (n = 45) showed increased expression of TIA-1 (55 versus 37%) and GrB (33 versus 9%) in T3NoMo-stage MF. Evaluation of multiple sequential biopsies from successive stages of MF also revealed an increase in the GrB/TIA-1 expression with tumor progression in five of eight cases. A clearcut relation between the expression of TIA-1 and/or GrB and the type of skin lesion biopsied was found. Considering all 74 biopsies, expression of TIA-1 and GrB was found in 18 of 50 (35%) and 5 of 50 (10%) patches or plaques, 9 of 16 (55%) and 3 of 16 (20%) tumors without blastic transformation, and 6 of 8 (75%) and 6 of 8 (75%) tumors with blastic transformation (defined as >50% blast cells). Correlation between GrB/TIA-1 expression in first diagnostic biopsies from patches or plaques from 40 patients with T2NoMo-stage MF and clinical follow-up data did not reveal differences in clinical behavior and survival between patients with (n = 14) or without (n = 26) expression of cytotoxic proteins, indicating that MF expressing cytotoxic proteins should not be considered as a separate group.

MeSH terms

  • Antigens, CD / metabolism
  • Disease Progression
  • Granzymes
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Membrane Proteins / biosynthesis*
  • Mycosis Fungoides / metabolism*
  • Mycosis Fungoides / mortality
  • Mycosis Fungoides / pathology
  • Poly(A)-Binding Proteins
  • Prognosis
  • Proteins*
  • RNA-Binding Proteins / biosynthesis*
  • Serine Endopeptidases / biosynthesis*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Rate
  • T-Cell Intracellular Antigen-1
  • T-Lymphocytes / metabolism*


  • Antigens, CD
  • Membrane Proteins
  • Poly(A)-Binding Proteins
  • Proteins
  • RNA-Binding Proteins
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases