Su I J, Chang I C, Cheng A L
Department of Pathology and Hematology/Oncology, National Taiwan University Hospital and College of Medicine, Taipei, R.O.C.
Ann Oncol. 1991 Feb;2 Suppl 2:151-5. doi: 10.1007/978-1-4899-7305-4_24.
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.
本研究旨在探讨高级别胸腺后T细胞恶性肿瘤侵袭性行为的生物学和分子基础。对以下三种肿瘤的新鲜冷冻组织进行研究：（1）人类T细胞白血病/淋巴瘤病毒I型（HTLV-I）阳性成人T细胞淋巴瘤（ATL）（7例）；（2）HTLV-I阴性侵袭性T细胞淋巴瘤（12例）；（3）HTLV-I阴性非侵袭性T细胞淋巴瘤（11例），采用免疫组织化学和Northern印迹杂交法检测几种生长相关基因或增殖抗原的表达，包括白细胞介素-2受体（IL-2R）、Ki-67、转化生长因子-β（TGF-β）、拓扑异构酶和多药耐药（MDR）基因。我们的结果显示，与非侵袭性T细胞淋巴瘤相比，与HTLV-I相关且具有间变性形态的肿瘤细胞中Ki-67、TGF-β和拓扑异构酶的表达增强。IL-2R的表达仅限于ATL和1例Ki-1淋巴瘤。MDR基因在ATL中频繁表达，但在其他HTLV-I阴性恶性肿瘤中很少表达。除Ki-67表达增加外，临床进展或复发与MDR的表达相关。因此，我们得出结论，高级别T细胞淋巴瘤的侵袭性临床行为可能主要源于肿瘤细胞的高增殖活性，但与HTLV-I的关联以及临床复发因耐药性的产生而更加复杂。
