Diebold J, Suchy B, Baretton G B, Blasenbreu S, Meier W, Schmidt M, Rabes H, Löhrs U
Pathological Institute, Ludwig Maximilians University, München, Germany.
Virchows Arch. 1996 Nov;429(4-5):221-7. doi: 10.1007/BF00198337.
There is increasing evidence that DNA ploidy is a prognostic factor in ovarian carcinomas, but it is uncertain whether MYC DNA amplification is an epiphenomenon of DNA nondiploidy or a distinct biological change with an impact on the clinical course of the disease. To clarify these issues we analysed DNA ploidy by flow and image cytometry and MYC copy number by polymerase chain reaction in archival material from ovarian carcinomas with known follow up. The results were compared with proliferative activity (Ki67 index) and p53 and bcl-2 expression. DNA cytometry revealed nondiploidy in 84 of 144 cases (58.3%). Nondiploidy was statistically significantly correlated with histological tumour type, histological grade, Ki67 index > 10%, FIGO stage, presence of residual tumour after debulking surgery and adverse postoperative outcome. Furthermore, DNA nondiploidy was associated with p53 accumulation. We found that 84.9% of the p53-positive cases were nondiploid. This points to the paramount importance of wild type p53 for the maintenance of genome integrity in this tumour type. MYC DNA amplification was seen in 33.8% (26/77 cases) of ovarian carcinoma. There was no correlation between MYC DNA amplification and histological tumour type, histological grade, FIGO stage, DNA ploidy, proliferative activity or prognosis. However, when p53 and bcl-2 expression was taken into account, a statistically significant correlation between gene alteration or expression patterns and histological tumour type was revealed. The group of mucinous carcinomas demonstrated both MYC DNA amplification and strong bcl-2 expression in 50% and contained the largest fraction of cases without aberration (37.5%). Endometrioid carcinomas were characterized by strong bcl-2 expression in 85%, whereas serous and undifferentiated carcinomas predominantly exhibited p53 alterations, frequently accompanied by bcl-2 overexpression or MYC DNA amplification. Thus, in interaction with other genes MYC DNA amplification may play a role in the determination of the varying differentiation patterns of ovarian carcinomas.
越来越多的证据表明，DNA倍性是卵巢癌的一个预后因素，但MYC DNA扩增是DNA非整倍体的一种附带现象，还是一种对疾病临床进程有影响的独特生物学变化，目前尚不确定。为了阐明这些问题，我们通过流式细胞术和图像细胞术分析了DNA倍性，并通过聚合酶链反应分析了已知随访情况的卵巢癌存档材料中的MYC拷贝数。将结果与增殖活性（Ki67指数）以及p53和bcl-2表达进行了比较。DNA细胞术显示，144例中有84例（58.3%）为非整倍体。非整倍体与组织学肿瘤类型、组织学分级、Ki67指数>10%、国际妇产科联盟（FIGO）分期、肿瘤细胞减灭术后残留肿瘤的存在以及不良术后转归在统计学上显著相关。此外，DNA非整倍体与p53蓄积有关。我们发现，84.9%的p53阳性病例为非整倍体。这表明野生型p53对于维持这种肿瘤类型的基因组完整性至关重要。在33.8%（26/77例）的卵巢癌中发现了MYC DNA扩增。MYC DNA扩增与组织学肿瘤类型、组织学分级、FIGO分期、DNA倍性、增殖活性或预后之间无相关性。然而，当考虑p53和bcl-2表达时，基因改变或表达模式与组织学肿瘤类型之间存在统计学上的显著相关性。黏液性癌组中50%的病例同时出现MYC DNA扩增和强烈的bcl-2表达，且无异常的病例比例最高（37.5%）。子宫内膜样癌的特征是85%的病例有强烈的bcl-2表达，而浆液性癌和未分化癌主要表现为p53改变，常伴有bcl-2过表达或MYC DNA扩增。因此，与其他基因相互作用时，MYC DNA扩增可能在决定卵巢癌不同的分化模式中起作用。
