Expression of growth-related genes and drug-resistance genes in HTLV-I-positive and HTLV-I-negative post-thymic T-cell malignancies.
This study was designed to investigate the biologic and molecular basis of the aggressive behavior of high-grade post-thymic T-cell malignancies. Freshly frozen tumor tissues from (1) human T-cell leukemia/lymphoma virus type I (HTLV-I)-positive adult T-cell lymphoma (ATL) (7 cases), (2) HTLV-I-negative aggressive T-cell lymphoma (12 cases), and (3) HTLV-I-negative nonaggressive T-cell lymphoma (11 cases) were studied for the expression of several growth-related genes or proliferation antigens including interleukin-2 receptor (IL-2R), Ki-67, transforming growth factor-beta (TGF-beta), topoisomerase, and the multidrug resistance (MDR) gene by immunohistochemistry and Northern blot hybridization. Our results showed that tumor cells associated with HTLV-I and anaplastic morphology had an enhanced expression of Ki-67, TGF-beta, and topoisomerase, as compared to nonaggressive T-cell lymphoma. The expression of IL-2R was limited to ATL and one Ki-1 lymphoma. The MDR gene was frequently expressed in ATL, but only infrequently in other, HTLV-I-negative, malignancies. Clinical progression or relapse was associated with the expression of MDR, in addition to an increased expression of Ki-67. We therefore conclude that the aggressive clinical behavior of high-grade T-cell lymphoma may result mainly from the high proliferative activity of tumor cells, but the association with HTLV-I and clinical relapse is further complicated by the development of drug resistance.
Su
I J
IJ
Department of Pathology and Hematology/Oncology, National Taiwan University Hospital and College of Medicine, Taipei, R.O.C.
Chang
I C
IC
Cheng
A L
AL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015152:Blotting, Northern; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics; D052118:Lysosomal-Associated Membrane Protein 1
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004264:DNA Topoisomerases, Type I; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1