title: Expression of cytotoxic proteins by neoplastic T cells in mycosis fungoides increases with progression from plaque stage to tumor stage disease.
abstract: 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.
authors.affiliation: Departments of Dermatology and Pathology, Free University Hospital, Amsterdam, The Netherlands. mh.vermeer@azvu.nl
authors.forename: M H
authors.initials: MH
authors.lastname: Vermeer
authors.forename: F A
authors.initials: FA
authors.lastname: Geelen
authors.forename: J A
authors.initials: JA
authors.lastname: Kummer
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: R
authors.initials: R
authors.lastname: Willemze
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018450:Disease Progression; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008565:Membrane Proteins / Q000096:biosynthesis*; D009182:Mycosis Fungoides / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D039102:Poly(A)-Binding Proteins; D011379:Prognosis; D011506:Proteins; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D000074019:T-Cell Intracellular Antigen-1; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases