De Vita S, Sansonno D, Dolcetti R, Ferraccioli G, Carbone A, Cornacchiulo V, Santini G, Crovatto M, Gloghini A, Dammacco F, Boiocchi M
Department of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy.
Blood. 1995 Sep 1;86(5):1887-92.
Hepatitis C virus (HCV) has been implicated as the major etiologic factor sustaining B-cell clonal expansion in type II mixed cryoglobulinemia (MC). A putative pathogenetic role of HCV in the development of MC-associated B-cell malignancies has also been speculated. We report for the first time the localization of HCV within a parotid non-Hodgkin's lymphoma (NHL) lesion in the course of HCV-related type II essential MC, an important step to implicate any infectious agent in the lymphomagenesis. Plus and minus strand HCV RNA was first demonstrated by polymerase chain reaction on the whole RNA from the lesion. Further immunohistochemical studies localized HCV c22 proteins in the residual ductal or acinar parotid structures, which also abnormally expressed HLA-DR antigens. Weak c22 signals were inconstantly detected in cells strictly confined around the residual epithelium, while all the remaining infiltrating cells in the parotid lesion stained c-22-negative. Staining for c33 and c100 HCV antigens was negative. In situ hybridization (ISH) studies again identified the residual parotid epithelial cells as the site of HCV infection and replication in the NHL lesion. Sialotropic viruses previously involved in lymphoproliferation, ie, Epstein-Barr virus and human herpesvirus-6, were absent in the same tissue lesion. According to the current models of B-cell lymphomagenesis, a role of HCV as an exogenous antigenic stimulus should be considered for NHL development in the present case, whereas malignant B cells do not appear permissive of active HCV replication. Further efforts would be worthwhile to clarify a role of HCV infection in the development of some B-cell malignancies.
丙型肝炎病毒（HCV）被认为是维持II型混合性冷球蛋白血症（MC）中B细胞克隆性扩增的主要病因。人们也推测HCV在MC相关B细胞恶性肿瘤的发生中具有假定的致病作用。我们首次报告了在HCV相关的II型原发性MC病程中，HCV在腮腺非霍奇金淋巴瘤（NHL）病变中的定位，这是将任何感染因子与淋巴瘤发生联系起来的重要一步。首先通过聚合酶链反应在病变的全RNA上证实了正负链HCV RNA的存在。进一步的免疫组织化学研究将HCV c22蛋白定位在残留的导管或腺泡腮腺结构中，这些结构也异常表达HLA-DR抗原。在严格局限于残留上皮周围的细胞中偶尔检测到微弱的c22信号，而腮腺病变中所有其余浸润细胞的c-22染色均为阴性。c33和c100 HCV抗原的染色为阴性。原位杂交（ISH）研究再次确定残留的腮腺上皮细胞是NHL病变中HCV感染和复制的部位。先前参与淋巴细胞增殖的亲唾液病毒，即爱泼斯坦-巴尔病毒和人类疱疹病毒6，在同一组织病变中不存在。根据目前的B细胞淋巴瘤发生模型，在本病例中，应考虑HCV作为外源性抗原刺激在NHL发生中的作用，而恶性B细胞似乎不允许HCV进行活跃复制。进一步努力阐明HCV感染在某些B细胞恶性肿瘤发生中的作用是值得的。
