探讨裸鼠人肝癌20年连续传代的病理变化特征。方法： 裸鼠人肝癌组织模型（SMMULTNM）连续观察20年（19872007年），皮下移植瘤传至228代，建立腹腔移植瘤、肝原位移植瘤及NODSCID小鼠肝原位移植瘤的病理资料，经光镜、电镜、图像分析、染色体分析、周围血液AFP检测等方法分析病理变化特征。结果： （1）上述4种肿瘤模型的局部侵袭和转移均长期存在：皮下移植瘤的局部侵袭率为59.70%(40/67)，肺内转移率为37.10%(23/62)；腹腔移植瘤的肺内转移率为59.02%(36/61)；肝原位移植瘤的肝内转移率为18.18%(4/22)，肺内转移率为31.82%(7/22)；NODSCID小鼠肝原位移植瘤的肺内转移率为53.85%。（2）皮下移植瘤的组织学变化：第10代前的瘤细胞分化和组织结构与原人肝癌近似，以Ⅱ级分化、粗梁型为主；第11代至225代瘤细胞以分化Ⅲ级、团块型为主，电镜下亦证实瘤细胞分化更差。（3）AFP检测第32代前为92 500 μg/L，第33代至130代AFP下降为6 729 μg/L，220代AFP检测为1 000~5 000 μg/L。（4）腹腔移植瘤的瘤细胞群体与肺转移瘤的瘤细胞群体DNA含量分布范围明显增宽，2C~6C不等，峰值明显右移，前者的分布范围比后者更宽；DNA含量分别为2.60±0.20和2.10±0.26。（5）染色体检测，第55~206代（相隔12年）部分瘤细胞染色体变为裸鼠染色体。结论： 裸鼠皮下移植瘤可连续传代20年，局部侵袭及转移的恶性生物学行为不变；瘤细胞分化更差，AFP下降，部分瘤细胞染色体变为裸鼠染色体。这些病理变化可能与裸鼠内环境影响和瘤细胞的多潜能分化有关。

To investigate the pathological changes of human hepatocellular carcinoma (HCC) after continuous passaging in nude mice. Methods: The mice model of HCC SMMULTMN were continuously observed for 20 years (19872007) . The subcutaneously transplanted carcinoma had been passaged for 228 generations. The pathological data of abdominally transplanted HCC, orthotopically transplanted HCC in nude mice, and orthotopically transplanted HCC in NODSCID mice were recorded. The pathological studies were conducted by light microscope, electron microscope, image analysis, chromosomal analysis, and measurement of alphafetoprotein (AFP) in peripheral blood. Results: (1) The local invasion and metastasis of of tumors were present in all the above 4 models for a long time. The local invasion rate and the pulmonary metastasis rate of subcutaneously transplanted tumors were 59.70% (40/67) and 37.10% (23/62), respectively. The pulmonary metastasis rate of abdominally transplanted tumors was 59.02%(36/61). The intrahepatic and pulmonary metastasis rate of the othotopically transplanted tumors were 18.18%(4/22) and 31.82% (7/22), respectively. The pulmonary metastasis rate of HCC in NODSCID mice was 53.85%. (2) The tissue structure and the differentiation of the 10th generation tumor cells was similar to those of primary HCC, with grade 2 differentiation and coarse trabecular pattern as the main characteristics. From the 11th generation to the 228th generation, the main characteristics of tumor cells were grade 3 differentiation and lump pattern. Electron microscope also showed worse differentiation. (3)The AFP level was 92 500 μg/L in cells before the 32th generation; it decreased to 6 729μg/L from the 33th130th generation cells; and the level of the 220th generation was 1 0005 000 μg/L.（4）The DNA contents had a wide distribution (from 2c to 6c) in abdominally transplanted tumors and the pulmonary metastatic tumors; the mean DNA index in the former tumors (2.60±0.20) was wider than the that in the latter (2.10±0.26) . (5)From the 55th generation to 206th generation, it was found that tumor cells had integrated into the chromosome of the nude mice. Conclusion: The subcutaneously transplanted HCC in nude mice can be stably expressed for 20 years, with no change in the local invasion and metastasis ability of HCC. The differentiation of the tumor cells worsenes and the AFP level is decreased in the blood; some chromosome of tumor cells integrate into the chromosome of nude mice, which may be related to the internal environment of nude mice and the multipotential differentiation of the tumor cells.