McCann A H, Kirley A, Carney D N, Corbally N, Magee H M, Keating G, Dervan P A
Biotechnology Centre, University College Dublin, Belfield, Ireland.
Br J Cancer. 1995 May;71(5):981-5. doi: 10.1038/bjc.1995.189.
The present study reports on the frequency of MDM2 gene amplification and MDM2 protein expression in a series of 100 breast carcinomas and its association with accumulation of the p53 protein. Of the 100 cases, frozen samples for 82 cases were available for Southern blotting. Three of the 82 (4%) demonstrated MDM2 gene amplification of up to 6-fold. Immunohistochemical analysis of the formalin-fixed, paraffin-embedded tumours demonstrated that 7/97 (7%) had nuclear expression for MDM2 in 10-50% of the tumour cells (type 2 staining) and were denoted MDM2+. Two of the MDM2-amplified samples were MDM2+ with one of the two tumours also displaying type 2 p53 nuclear staining. Finally at the protein level, MDM2+ tumours were significantly associated with tumours having low levels of p53 staining (0-10% cells positive) (P = 0.03). We conclude that MDM2 gene amplification occurs at a lower frequency in breast cancer than in non-epithelial tumours. Alterations in MDM2 and p53 may represent alternative pathways in tumorigenesis, but they are not mutually exclusive in all cases.
本研究报告了100例乳腺癌中MDM2基因扩增和MDM2蛋白表达的频率及其与p53蛋白积累的关系。100例病例中，82例有冷冻样本可用于Southern印迹分析。82例中有3例（4%）显示MDM2基因扩增达6倍。对福尔马林固定、石蜡包埋肿瘤的免疫组织化学分析表明，97例中有7例（7%）肿瘤细胞的10%-50%有MDM2核表达（2型染色），被标记为MDM2+。2例MDM2基因扩增样本为MDM2+，其中1例肿瘤也显示2型p53核染色。最后在蛋白水平上，MDM2+肿瘤与p53染色水平低（0%-10%细胞阳性）的肿瘤显著相关（P = 0.03）。我们得出结论，MDM2基因扩增在乳腺癌中的发生频率低于非上皮性肿瘤。MDM2和p53的改变可能代表肿瘤发生的替代途径，但在所有情况下它们并非相互排斥。
