人原发性结肠恶性淋巴瘤裸小鼠原位移植肝转移模型的建立

目的 为探讨结肠恶性淋巴瘤的发病机制和实验治疗提供理想的动物模型。方法将结肠恶性淋巴瘤术中原发灶和肝转移灶新鲜瘤组织块植入裸小鼠结肠黏膜层内，观察原位移植的成瘤率，移植瘤的侵袭和转移率。进行形态学（光镜、电镜、免疫组织化学）、染色体核型和流式细胞分析。结果人结肠淋巴瘤原发灶和肝转移灶新鲜瘤组织均获得移植成功。依据WHO新的分类标准，建成1株人结肠原发性（原发灶）非霍奇金B细胞性恶性淋巴瘤裸鼠原位移植高转移模型（HCBL-0303）和1株人结肠原发性（肝转移灶）非霍奇金B细胞性恶性淋巴瘤裸鼠原位移植肝转移模型（HCBL-0304）。移植瘤组织病理学为（非霍奇金B细胞性）高度恶性淋巴瘤；免疫组化显示CDl9、CD20、CD22阳性，CD3、CD7阴性。染色体数目55—59条；流式细胞DI值1．59—1．71，均为异倍体。HCBL-0303肝转移率为63．7％，淋巴结转移率为56．4％；HCBL-0304肝转移率和淋巴结转移率为100％。移植瘤在裸鼠结肠内自主侵袭性生长，发生血液转移、淋巴转移和腹腔内种植性转移。结论HCBL-0303和HCBL-0304是首次成功建立的人结肠恶性淋巴瘤裸鼠原位移植自发性肝转移模型，可用于结肠恶性淋巴瘤的发病机制、侵袭、转移及实验治疗的研究。

Establishment of liver metastasis model of human primary colonic lymphoma by orthotopic transplantation

OBJECTIVE: To provide an ideal animal model for exploring pathogenesis and experimental treatment of primary colonic lymphoma. METHODS: Primary colonic and liver metastatic lymphoma tissues were obtained from the surgical specimens,and transplanted into colonic mucosa of nude mice respectively. The tumorigenesis, invasion, metastasis and morphology of the transplanted tumor were observed. Karyotype was analyzed and DNA content was measured. RESULTS: According to the new WHO classification of malignant lymphoma, two high metastatic models (HCBL-0303 from primary lymphoma and HCBL-0304 from live metastatic lesion) of human primary colonic non-Hodgkin's B cell lymphoma in nude mice were established successfully by orthotopic transplantation. Pathological examination showed poorly differentiated non-Hodgkin's B cell lymphoma of the transplanted tumors, and immunohistochemical staining showed positive expressions of CD19, CD20 and CD22, and negative expressions of CD3 and CD7. The number of chromosome ranged from 55 to 59, and DNA index (DI) was 1.59 - 1.71 (i.e. heteroploid). In HCBL-0303,liver metastasis rate was 63.7% and lymph node metastasis rate was 56.4%. However, in HCBL-0304, both metastasis rates of liver and lymph node were 100%. The transplanted tumors grew autonomously and invasively in nude mice, and further developed hematogenous, lymphatic metastasis and intrapreritoneal seeding. CONCLUSIONS: HCBL-0303 and HCBL-0304 are the first established high metastatic models of primary colonic lymphoma, and can be applied to the research on pathogenesis, invasion,metastasis and experimental therapy of human primary colonic lymphoma.