ACCUMULATION OF NUCLEAR P53 AND TUMOR PROGRESSION IN BLADDER-CANCER
ACCUMULATION OF NUCLEAR P53 AND TUMOR PROGRESSION IN BLADDER-CANCER
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DOI：
10.1056/nejm199411103311903
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发表时间：
1994-11-10
影响因子：
158.5
通讯作者：
COTE, RJ
中科院分区：
文献类型：
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作者：
ESRIG, D;ELMAJIAN, D;COTE, RJ
背景我们以前已经证明了一个强有力的协会之间的核积累的p53蛋白，通过免疫组化分析，并在p53基因突变。本研究旨在探讨膀胱移行细胞癌中p53蛋白的核积聚与肿瘤进展的关系。对243例经根治性膀胱切除术后的膀胱移行细胞癌（Pa期，非浸润性疾病，P4期，直接侵犯邻近器官或结构的疾病）的组织标本进行了p53蛋白的免疫组化检测。然后分析核p53反应性与复发时间和总生存率的关系。核p53的检测与膀胱癌复发风险的增加（P < 0.001）和总生存率的降低（P < 0.001）显著相关。在局限于膀胱的癌症患者中，P1、P2和P3a期肿瘤在5年内没有可检测到的核p53反应性的复发率分别为7%、12%和11%，而具有p53免疫反应性的肿瘤的复发率分别为62%、56%和80%。当研究肿瘤细胞核中p53的存在或不存在与总生存率的关系时，也得到了类似的结果。在根据分级、病理分期和淋巴结状态分层的多变量分析中，核p53状态是复发和总生存率的独立预测因子（在局限于膀胱的癌症中，是唯一的独立预测因子）（P < 0.001）。在局限于膀胱的移行细胞癌患者中，通过免疫组织化学方法检测到肿瘤细胞核中p53的积聚预示复发和死亡的风险显著增加，与肿瘤分级、分期和淋巴结状态无关。局限于膀胱的移行细胞癌患者，如果表现出核p53反应性，应考虑辅助治疗方案。
Background. We have previously demonstrated a strong association between nuclear accumulation of p53 protein, as determined by immunohistochemical analysis, and mutations in the p53 gene. The purpose of this study was to determine the relation between nuclear accumulation of p53 and tumor progression in transitional-cell carcinoma of the bladder.Methods. Histologic specimens of transitional-cell carcinoma of the bladder (stages Pa, noninvasive disease, to P4, disease with direct extension into adjacent organs or structures) from 243 patients who were treated by radical cystectomy were examined for the immunohistochemical detection of p53 protein. Nuclear p53 reactivity was then analyzed in relation to time to recurrence and overall survival.Results. The detection of nuclear p53 was significantly associated with an increased risk of recurrence of bladder cancer (P < 0.001) and with decreased overall survival (P < 0.001). In patients with cancer confined to the bladder, the rates of recurrence for stage P1, P2, and P3a tumors that had no detectable nuclear p53 reactivity at five years were 7, 12, and 11 percent, respectively, as compared with 62, 56, and 80 percent, respectively, for tumors that had p53 immunoreactivity. Similar results were obtained when the presence or absence of p53 in the nuclei of the tumor cells was studied in relation to overall survival. In a multivariable analysis stratified according to grade, pathological stage, and lymph-node status, nuclear p53 status was an independent predictor (and in cancer confined to the bladder, the only independent predictor) of recurrence and overall survival (P < 0.001).Conclusions. In patients with transitional-cell carcinoma confined to the bladder, an accumulation of p53 in the tumor-cell nuclei detected by immunohistochemical methods predicts a significantly increased risk of recurrence and death, independently of tumor grade, stage, and lymph-node status. Patients with transitional-cell carcinoma confined to the bladder that demonstrates nuclear p53 reactivity should be considered for protocols of adjuvant treatment.