Picker L J, Medeiros L J, Weiss L M, Warnke R A, Butcher E C
Department of Pathology, Stanford University School of Medicine, California.
Am J Pathol. 1988 Mar;130(3):496-504.
In man, lymphocyte binding to high endothelial venules (HEVs) involves specific 85-95 kd cell surface glycoprotein(s) recognized by the monoclonal antibodies Hermes-1 and Hermes-3. These putative "homing receptor" molecule(s) are believed to play an important role in the normal regulation of lymphocyte circulation. To investigate the possibility that homing receptors also play a role in the biology of lymphoid malignancies, the authors studied over 300 cases of non-Hodgkin's lymphoma by immunohistologic staining with Hermes-1 and -3, antibodies that define two distinct epitopes on the gp 85-95 putative homing receptor molecules. Furthermore, they directly compared expression of the Hermes-3 antigen with clinical extent of disease in 57 patients with diffuse large cell lymphoma. They found that staining of the various subtypes of lymphoma was heterogeneous, and in general correlated with patterns of expression seen in benign lymphoid populations. Essentially all normal lymphoid populations examined, except germinal center B cells and most cortical thymocytes, bear a high level of homing receptor antigen. Similarly, nearly all peripheral T-cell lymphomas, diffuse small cell lymphomas of B lineage, and plasma cell tumors were positive for homing receptor antigen (95%, 97%, and 100%, respectively). Small noncleaved cell, follicular, and diffuse large cell lymphomas of B lineage, tumors having morphologic or immunologic features resembling germinal center cells, frequently failed to express Hermes-defined epitopes (81%, 41%, 25% Hermes-3-, respectively). Antigen expression in T-lymphoblastic lymphomas strongly correlated with immunophenotypic subtypes: only 8% of CD4+/CD8+ were Hermes-1+ versus 86% of CD4-/CD8- and 43% of CD4+/CD8-. Hermes-3 expression by cases of diffuse, large cell lymphoma which showed generalized lymph node involvement (a pattern strongly suggestive of HEV-mediated spread; 100% Hermes-3+, mean intensity 3.4) was higher than that of cases with localized or multifocal, contiguous involvement (consistent with lymphatic spread; 69% Hermes-3+, mean intensity 2.2), but these differences did not achieve statistical significance. The results indicate that homing receptor antigen expression, although perhaps necessary for wide-spread blood-borne lymphoma dissemination to lymphoid sites, is not in and of itself sufficient to predict such behavior in this subtype of lymphoid malignancy.
在人类中,淋巴细胞与高内皮微静脉(HEV)的结合涉及单克隆抗体Hermes-1和Hermes-3识别的特定85 - 95kd细胞表面糖蛋白。这些假定的“归巢受体”分子被认为在淋巴细胞循环的正常调节中起重要作用。为了研究归巢受体是否也在淋巴恶性肿瘤生物学中发挥作用,作者用Hermes-1和-3进行免疫组织化学染色,研究了300多例非霍奇金淋巴瘤病例,这两种抗体可界定gp 85 - 95假定归巢受体分子上的两个不同表位。此外,他们直接比较了57例弥漫性大细胞淋巴瘤患者中Hermes-3抗原的表达与疾病的临床范围。他们发现淋巴瘤各亚型的染色是异质性的,总体上与良性淋巴群体中所见的表达模式相关。除生发中心B细胞和大多数皮质胸腺细胞外,基本上所有检查的正常淋巴群体都有高水平的归巢受体抗原。同样,几乎所有外周T细胞淋巴瘤、B系弥漫性小细胞淋巴瘤和浆细胞瘤的归巢受体抗原均为阳性(分别为95%、97%和100%)。B系小无裂细胞、滤泡性和弥漫性大细胞淋巴瘤,具有类似于生发中心细胞形态或免疫特征的肿瘤,常常不表达Hermes界定的表位(分别为81%、41%、25% Hermes-3阴性)。T淋巴母细胞淋巴瘤中的抗原表达与免疫表型亚型密切相关:只有8%的CD4+/CD8+为Hermes-1阳性,而CD4-/CD8-为86%,CD4+/CD8-为43%。表现为全身淋巴结受累(一种强烈提示HEV介导扩散的模式;100% Hermes-3阳性,平均强度3.4)的弥漫性大细胞淋巴瘤病例的Hermes-3表达高于局限性或多灶性、连续性受累(符合淋巴扩散;69% Hermes-3阳性,平均强度2.2)的病例,但这些差异无统计学意义。结果表明,归巢受体抗原表达虽然可能是广泛血行性淋巴瘤扩散至淋巴部位所必需的,但就其本身而言不足以预测这种淋巴恶性肿瘤亚型中的此类行为。