Studies of Clinical Diagnosis and Treatment on Cutaneous T-Cell Lymphoma

皮肤T细胞淋巴瘤的临床诊治研究

• 批准号: 63570473
• 负责人: NAKAJIMA Hiroshi
• 金额: $ 1.34万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570473/
• 关键词: cutaneous T-cell lymphoma; mycosis fungoids; helper T-cell; Th1; Th2; naive T cell; memory T cell; interferon gamma; 09adhesion molecule; T hl; T h2; helperT細胞; T_<h1>; T_<h2>; interferon-γ; naivi T cell; CTCL; ATL; T細胞受容体; CD7; PUVA /

(1) We studied surface markers presents in lymphoma of the skin by immunohistochemical staining, using the ABP (avidine-biotin-peroxidase complex) methods and PAP (peroxidase-anti-peroxidase complex) methods. 80 percent of T-cell lymphoma except ATL analyzed by the ABP methods showed a helper/inducer phenotype (Leu2a~, Leu3a^+), 6 percent showed a suppressor/cytotoxic phenotype (Leu2a^+, Leu3a~), one case showed an inducer phenotype, one case showed a phenotype of so-called Ki-1 lymphoma. These results showed that T-cell lymphoma of the skin is heterogeneous in nature. In other words, CTCL is one type but represents a major propotion of T-cell lymphomas of the skin. (2) An important disease entity distinct from cutaneous T-cell lymphoma in Japan is adult T-cell leukemia/lymphoma, which usually shows the same phenotype as CTCL, i. e., a helper/inducer T-cell phenotype, and usually involves the skin. Clinically, both CTCL and ATL are heterogeneous in nature. So, we demonstrated differenc … More es between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant clinical findings were peripheral lymph node involvement, skin lesions, hepatosplenomegary, leukemic manifestations, and an aggressive course. In patients with CTCL, by contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was demonstrated. Phenotypic heterogeneity of ATL in the skin, i. e., CD4^-CD8^-, CD4^+CD8^-, and CD4^-CD8^+, was demonstrated. Expression of Leu8, CD7 (Leu9), and CD45RA (2H4) was high in both the skin-infiltrating ATL cells and peripheral blood and lymph node ATL cells compared with that in the skin-infiltrating CTCL cells. Expression of CD25 (IL-2R), CD71 (OKT9), HLA-DR, and HLA-DQ was high, and that of CD45RO (UCHL-1) was not significantly high in the skin-infiltrating CTCL cells compared with that in ATL cells. The most significant phenotype difference between ATL cells and CTCL cells was the expression of Leu8 (lymph node homing receptor), CD7 and CD25 antigens on the cell surface, and the main phenotypic difference between skin-infiltrating ATL and CTCL cells and peripheral blood and lymph node ATL cells was the expression of CD29 and CD45RA. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL, and suggest that the predominant phenotype of peripheral blood and lymph node ATL cells is that of naive, relatively immature or activated T-cells, and that CTCL cells are previously activated (memory) T-cells. In other words, CTCL cells do not share the same origin as ATL cells. These observations support the concept that ATL ia a disease distinct from CTCL. (3) The expression of PC (Ki-67) antigen, DNA polymerase-alpha and trasferrin receptor (OKT9 : CD71) were studied in 29 cases of cutaneous T-cell lymphomas and in a variety of benign cutaneous lymphoid infiltrates by immunohistochemistry. PCBeside, correlation with histologic grading of lymphomas and expression of those antigens on lymphoid cells was indicated : the high-grade types, e. g., immunoblastic type, exhibited greater positivity than intermediate grade types and much more than low-grade types. (4) We investigated the pretreatment characteristics and prognosis of T-cell lymphoma, including mycosis fungoids, T-cell lymphoma of the skin other than MF, and B-cell lymphoma of the skin. Percentage of CD3-positive cell and CD4-positive cell in the peripheral blood lymphocytes was one of the most useful prognostic factor. TNM staging of CTCL and international working formulation were also useful factor for prognosis. Less

(1)我们使用ABP（亲和素-生物素-过氧化物酶复合物）方法和PAP（过氧化物酶-抗过氧化物酶复合物）方法通过免疫组织化学染色研究了皮肤淋巴瘤中存在的表面标志物。通过ABP方法分析，除ATL外，80%的T细胞淋巴瘤显示辅助/诱导表型（Leu2a~、Leu3a^+），6%显示抑制/细胞毒性表型（Leu2a^+、Leu3a~），1例显示诱导表型，1例显示所谓Ki-1淋巴瘤的表型。这些结果表明皮肤 T 细胞淋巴瘤本质上是异质的。换句话说，CTCL 是一种类型，但代表了皮肤 T 细胞淋巴瘤的主要部分。 (2) 在日本，一种与皮肤 T 细胞淋巴瘤不同的重要疾病实体是成人 T 细胞白血病/淋巴瘤，通常表现出与 CTCL 相同的表型，即成人 T 细胞白血病/淋巴瘤。例如，辅助/诱导 T 细胞表型，通常涉及皮肤。临床上，CTCL 和 ATL 本质上是异质的。因此，我们证明了 CTCL 和 ATL 在临床和免疫病理学细胞表面特征方面的差异。在 ATL 患者中，主要的临床表现是周围淋巴结受累、皮肤病变、肝脾肿大、白血病表现和侵袭性病程。相比之下，CTCL 患者在发病时仅以皮肤病变为主，预后相对较好。皮肤中 ATL 的表型异质性，i。例如，CD4^-CD8^-、CD4^+CD8^- 和 CD4^-CD8^+ 已被证明。与皮肤浸润 CTCL 细胞相比，皮肤浸润 ATL 细胞以及外周血和淋巴结 ATL 细胞中 Leu8、CD7 (Leu9) 和 CD45RA (2H4) 的表达均较高。与ATL细胞相比，皮肤浸润CTCL细胞中CD25（IL-2R）、CD71（OKT9）、HLA-DR和HLA-DQ的表达较高，而CD45RO（UCHL-1）的表达不显着高。 ATL细胞与CTCL细胞最显着的表型差异是细胞表面Leu8（淋巴结归巢受体）、CD7和CD25抗原的表达，皮肤浸润ATL和CTCL细胞与外周血和淋巴结ATL细胞的主要表型差异是CD29和CD45RA的表达。这些发现证实，细胞表面抗原表达的差异可能反映了ATL和CTCL的临床特征，并表明外周血和淋巴结ATL细胞的主要表型是幼稚的、相对不成熟的或活化的T细胞，而CTCL细胞是先前活化的（记忆）T细胞。换句话说，CTCL细胞与ATL细胞并不具有相同的起源。这些观察结果支持 ATL 是一种与 CTCL 不同的疾病的概念。 (3)采用免疫组化方法研究了29例皮肤T细胞淋巴瘤和多种良性皮肤淋巴浸润组织中PC(Ki-67)抗原、DNA聚合酶-α和转铁蛋白受体(OKT9:CD71)的表达。 PCB此外，还表明了淋巴瘤的组织学分级和淋巴细胞上这些抗原的表达的相关性：高级别类型，例如。例如，免疫母细胞类型，表现出比中级类型更高的阳性率，并且比低级类型更高的阳性率。 (4)探讨T细胞淋巴瘤的治疗前特点及预后，包括蕈样肉芽肿、除MF外的皮肤T细胞淋巴瘤、皮肤B细胞淋巴瘤。外周血淋巴细胞中CD3阳性细胞和CD4阳性细胞的百分比是最有用的预后因素之一。 CTCL的TNM分期和国际工作方案也是预测预后的有用因素。较少的

项目成果

Tetsuo Nagatani et al: "Comparative study of cutaneous Tーcell lymphoma and adult Tーcell lymphoma/leukemia" Cancer. 66. 2380-2386 (1990)

Tetsuo Nagatani 等人：“皮肤 T 细胞淋巴瘤和成人 T 细胞淋巴瘤/白血病的比较研究”癌症 66. 2380-2386 (1990)。

Tetsuo Nagatani et al: "Clinical and immunohistochemical analysis of skin lymphoma in Japan"

Tetsuo Nagatani 等人：“日本皮肤淋巴瘤的临床和免疫组织化学分析”

Tetsuo Nagatani: "Conparisons of Clinical,morphologic and immanohistochemical Chavactevistics of Citanecus T-cell lymphoma and adult T-cell lsukemia/lymphoma" J.Invest.Dermatol.92. 487 (1989)

Tetsuo Nagatani：“Citanecus T 细胞淋巴瘤和成人 T 细胞白血病/淋巴瘤的临床、形态学和免疫组织化学 Chavactevistics 的比较”J.Invest.Dermatol.92。

Tetsuo Nagatani et al: "Adult Tーcell leukemia/lymphomaーthe clinical,histochemical,immunologic and immunohistochemical characteristics" Proceedings of the Sixth JapanーKorea joint meeting of Dermatology. 63. 463-646 (1990)

Tetsuo Nagatani 等：“成人 T 细胞白血病/淋巴瘤 - 临床、组织化学、免疫学和免疫组织化学特征”第六届日韩皮肤病学联席会议记录 63. 463-646 (1990)。

Hiroshi NAKAJIMA: "Malignant lymphoma of the skin - especially cutaneous T-cell lymphoma" The Japanese Journal of Dermatology. 100 (13). 1336-1388 (1990)

Hiroshi NAKAJIMA：“皮肤恶性淋巴瘤 - 特别是皮肤 T 细胞淋巴瘤”《日本皮肤病学杂志》。