Vet J A, Bringuier P P, Poddighe P J, Karthaus H F, Debruyne F M, Schalken J A
Department of Urology, University Hospital, Nijmegen, The Netherlands.
Br J Cancer. 1994 Sep;70(3):496-500. doi: 10.1038/bjc.1994.334.
Evidence is accumulating that the tumour-suppressor gene p53 is involved in the development of bladder cancer. Therefore we studied p53 mutations in 47 bladder cancers obtained from 45 patients using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Eight out of 24 invasive tumours appeared to have a p53 mutation, while no p53 mutations were found in the superficial tumours. All the p53 mutations were found in grade 3 tumours. The tumours with altered p53 showed a higher frequency of allelic loss (FAL) than the tumours without a mutation (55.8% vs 21.1%, P < 0.05, chi 2 test). This increase in FAL suggests a correlation between p53 mutations and genetic instability. A significant correlation between mutated p53 and poor survival in the whole group studied was found (P < 0.001, log-rank test). However, within the group of muscle-invasive tumours the occurrence of p53 mutations had no additional prognostic value. Therefore, even though p53 mutations were found in aggressive tumours, the clinical usefulness of its detection seems limited. Nevertheless, these results imply that p53 is involved in the clinical behaviour of bladder cancer; its role in the progression of superficial cancer to invasive disease merits further attention.
越来越多的证据表明,肿瘤抑制基因p53与膀胱癌的发生发展有关。因此,我们采用聚合酶链反应-单链构象多态性(PCR-SSCP)分析,对45例患者的47例膀胱癌进行了p53突变研究。24例浸润性肿瘤中有8例似乎存在p53突变,而浅表性肿瘤中未发现p53突变。所有p53突变均见于3级肿瘤。p53改变的肿瘤比未发生突变的肿瘤等位基因缺失频率(FAL)更高(55.8%对21.1%,P<0.05,卡方检验)。FAL的增加表明p53突变与基因不稳定之间存在相关性。在所研究的整个组中,发现突变型p53与较差的生存率之间存在显著相关性(P<0.001,对数秩检验)。然而,在肌肉浸润性肿瘤组中,p53突变的发生没有额外的预后价值。因此,尽管在侵袭性肿瘤中发现了p53突变,但其检测的临床实用性似乎有限。尽管如此,这些结果表明p53参与了膀胱癌的临床行为;其在浅表癌向浸润性疾病进展中的作用值得进一步关注。