Schumacher U, Adam E, Dietl J, Horny H P
University of Southampton, United Kingdom.
Exp Mol Pathol. 1997 Apr;64(2):103-13. doi: 10.1006/exmp.1997.2213.
Human ovarian malignancies from three different patients (histology: two serous cystadenocarcinomata and one mixed Müllerian tumor, homologous type) were successfully serially transplanted intraperitoneally into severe combined immunodeficient (SCID) mice where the tumor cells spread around the peritoneal cavity. If the ascites derived from cystadenocarcinoma cells engrafted in the female genital tract of the SCID mice, they formed cystic tumors resembling remarkably well the original tumors in the patients. Immunohistochemical analysis revealed that the immunophenotype of the patients' original tumor and those grown in SCID mice were similar in the case of the two cystadenocarcinomata; in addition, the marker expression in general was stable during serial transplantation. If distant metastases occurred in the lungs, they immunophenotypically resembled those grown intraperitoneally. In contrast, the cells derived from the mixed Müllerian tumor shifted during serial transplantation from a spindle cell morphology toward a morphology characterized by cuboidal cells. The transition toward a more epithelial phenotype was accompanied by a changed immunophenotype of the tumor cells which became positive for epithelial cell markers such as carcinoembryonic antigens, CA 19-9 and CA 125. Concurrently with this differentiation, the p53 immunophenotype changed from positive to negative, indicating a further mutation in the p53 gene during serial passages.
来自三名不同患者的人类卵巢恶性肿瘤(组织学类型:两例浆液性囊腺癌和一例同源性混合苗勒管肿瘤)成功地经腹腔连续移植到严重联合免疫缺陷(SCID)小鼠体内,肿瘤细胞在腹腔内扩散。如果源自囊腺癌细胞的腹水植入SCID小鼠的女性生殖道,就会形成囊性肿瘤,与患者的原始肿瘤极为相似。免疫组织化学分析显示,在两例浆液性囊腺癌病例中,患者原始肿瘤和在SCID小鼠体内生长的肿瘤的免疫表型相似;此外,在连续移植过程中,标志物表达总体上是稳定的。如果发生肺远处转移,其免疫表型与腹腔内生长的肿瘤相似。相比之下,源自混合苗勒管肿瘤的细胞在连续移植过程中从梭形细胞形态转变为以立方形细胞为特征的形态。向更上皮样表型的转变伴随着肿瘤细胞免疫表型的改变,这些细胞对癌胚抗原、CA 19-9和CA 125等上皮细胞标志物呈阳性。在这种分化的同时,p53免疫表型从阳性变为阴性,表明在连续传代过程中p53基因发生了进一步突变。