EXPRESSION OF CYTOTOXIC MOLECULES IN INTESTINAL T-CELL LYMPHOMAS

Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from ap intraepithelial T-l ymphocytes. Since these lymphocytes may contain cytotoxic molecules, t he question of whether this also holds true for ITCL arises. Twenty IT CL cases were examined for the presence df granzyme B, perforin, and;T -cell-restricted-intracellular antigen (TIA-l)/granule membrane protei n of 17 kD (GMP-17). Two molecules with restricted expression in cytot oxic cells, granzyme B and perforin, were detected by immunocytochemis try and by in situ hybridization with an isotopically labelled RNA pro be, respectively. Immunocytochemistry was also performed with the anti body 2G9, which recognizes two molecules, one expressed by cytotoxic c ells (TIA-1) and the other found in granulocytes and cytotoxic cells ( GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neop lastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectivel y, of ITCL, but not in the tumour cells of the control group, which co nsisted of intestinal B-cell lymphomas (five cases) and CD8-negative p eripheral nodal T-cell lymphomas (six cases). At least one of these mo lecules was expressed in the tumour cells of all ITCL cases. 2G9 prove d to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cas es, but also found in high numbers of neoplastic cells in positive cas es. In conclusion, ITCL appears to show cytotoxic differentiation in a ll cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithel ial ap cytotoxic T-lymphocytes. (C) 1997 by John Wiley & Sons, Ltd.