Soong R, Knowles S, Williams K E, Hammond I G, Wysocki S J, Iacopetta B J
Department of Surgery, University of Western Australia, Nedlands, Australia.
Br J Cancer. 1996 Aug;74(4):562-7. doi: 10.1038/bjc.1996.401.
The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of these changes. Of 122 endometrial carcinomas, 33 (27%) showed overexpression of p53 in the nucleus and 66 (54%) in the cytoplasm. Mutation in the p53 gene was found in 16 (13%) cases but showed no significant association with patient survival. Nuclear p53 overexpression was associated with poor survival (48% vs 80% alive in negative tumours 5 years post operatively, P < 0.001). In contrast, cytoplasmic p53 overexpression was associated with better survival (85% vs 55%, P < 0.001). When patients were separated into prognostic subgroups according to established clinical markers, these associations remained significant within most subgroups examined. In multivariate analysis adjusted for surgical stage, histological grade and type and vascular invasion, both nuclear p53 overexpression [hazard ratio 4.9 (95% CI 1.3-17.6). P = 0.016] and cytoplasmic overexpression [0.25 (0.06-0.98), P = 0.047] were independent prognostic factors. Immunohistochemical assessment of p53 overexpression in the nucleus and cytoplasm could provide useful prognostic information for the management of patients with endometrial cancer.
p53基因在肿瘤进展及细胞对DNA损伤的反应中发挥着重要作用，这促使人们对该基因改变的临床意义展开研究。我们检测了子宫内膜癌中p53基因的过表达及突变情况，以评估这些变化的预后意义。在122例子宫内膜癌中，33例（27%）显示细胞核p53过表达，66例（54%）显示细胞质p53过表达。在16例（13%）病例中发现了p53基因突变，但该突变与患者生存率无显著关联。细胞核p53过表达与较差的生存率相关（术后5年，阴性肿瘤患者的生存率为80%，而阳性患者为48%，P<0.001）。相反，细胞质p53过表达与较好的生存率相关（85%对55%，P<0.001）。当根据既定的临床指标将患者分为预后亚组时，在大多数检测的亚组中，这些关联仍然显著。在对手术分期、组织学分级和类型以及血管侵犯进行校正的多变量分析中，细胞核p53过表达[风险比4.9（95%CI 1.3 - 17.6），P = 0.016]和细胞质过表达[0.25（0.06 - 0.98），P = 0.047]均为独立的预后因素。通过免疫组织化学评估细胞核和细胞质中p53的过表达情况可为子宫内膜癌患者的管理提供有用的预后信息。
