CD26 (dipeptidyl peptidase IV/DPP IV) as a novel molecular marker for differentiated thyroid carcinoma

Abstract

In this report we show that CD26 (dipeptidyl peptidase IV/DPP IV) is a novel molecular marker for differentiated thyroid carcinoma. Northern-blot analysis of 22 various thyroid tissues revealed that CD26 is a more specific marker of differentiated thyroid carcinoma than 3 proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2 and EGF-R. A comparative study of 3 CD26 assays, Northern blotting, immunohistochemical staining and activity staining clearly showed that CD26 enzyme activity staining is the most specific assay for differentiated thyroid carcinoma, yet the easiest to perform. Activity staining of 216 thyroid tissues detected CD26 in all 52 papillary carcinomas and all 5 follicular carcinomas, while all 58 cases of Graves' disease were CD26-negative. Among benign neoplasms, 54 of 55 adenomatous goiters and 29 of 33 follicular adenomas were CD26 negative. Staining intensity of the enzyme activity was relative to the degree of CD26 mRNA expression. Southern-blot study showed no gene amplification or major translocation of the CD26 gene in 7 papillary carcinomas examined. Based on this study, ectopic expression of CD26 in differentiated thyroid carcinomas is thought to be mainly caused by increased CD26 mRNA expression. In conclusion, CD26 activity staining is a simple, specific assay which should be added to the usual pathological examinations in order to distinguish differentiated thyroid carcinomas from benign thyroid diseases.

Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells

“…One of these ectoenzymes, dipeptidylpeptidase IV (DPPIV) assigned to CD26, may be considered as a useful marker in some diseases. Overexpression of CD26 is observed in dierentiated thyroid (Tanaka et al, 1995) and liver (Stecca et al, 1997) carcinoma, on blood T cells from patients with autoimmune diseases (Ha¯er et al, 1985;Eguchi et al, 1989;Nakao et al, 1989) and in B cell chronic lymphocytic leukemia (B-CLL) (Bauvois et al, 1999). In contrast, the loss of CD26 has been associated with T-CLL and ALL (Kondo et al, 1996) and melanoma progression (Wesley et al, 1999).…”

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

“…Additionally, its DPPIV enzyme activity has a key role in various aspects of T-cell activation, as demonstrated by studies using DPPIV inhibitors, soluble CD26/DPPIV molecules or CD26 genetic mutants (Flentke et al, 1991;Tanaka et al, 1993Tanaka et al, , 1994Steinbrecher et al, 2001). Besides its involvement in normal T-cell function, CD26 may also have a role in the development of certain tumors (Tanaka et al, 1995;Stecca et al, 1997;Bauvois et al, 1999;Dang and Morimoto, 2002). For example, it is expressed on the surface of such aggressive T-cell malignancies as T-cell lymphoblastic lymphomas/ acute lymphoblastic leukaemias and T cell CD30+ anaplastic large cell lymphomas, but not on the more indolent T-cell diseases like mycosis fungoides (Carbone et al, 1995;Jones et al, 2001).…”

Constitutive expression of CD26/dipeptidylpeptidase IV on peripheral blood B lymphocytes of patients with B chronic lymphocytic leukaemia

“…Overexpression of CD26/DPP IV was observed in differentiated thyroid carcinomas (Tanaka et al, 1995) and on T blood cells from patients with autoimmune diseases including progressive multiple sclerosis, GravesÕ disease and rheumatoid arthritis (Hafler et al, 1985;Eguchi et al, 1989;Nakao et al, 1989). In contrast, the loss of CD26/DPP IV molecule from the surface of T-cells has been associated with T-CLL (chronic lymphocytic leukaemia) and ALL (acute lymphocytic leukaemia) diseases (Kondo et al, 1996), oral cancer (Uematsu et al, 1996) and HIV infection .…”