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细胞周期蛋白依赖性激酶抑制剂p27Kip1的表达及肿瘤细胞凋亡对非早期胃癌患者总生存期的影响

Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma.

作者信息

Ohtani M, Isozaki H, Fujii K, Nomura E, Niki M, Mabuchi H, Nishiguchi K, Toyoda M, Ishibashi T, Tanigawa N

机构信息

Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Japan.

出版信息

Cancer. 1999 Apr 15;85(8):1711-8.

PMID:10223564
Abstract

BACKGROUND

The expression of p27Kip1 and apoptosis have been implicated in tumor aggressiveness and proved to be prognostic predictors for several human malignancies. In this study, the authors sought to investigate the expression of p27Kip1 and apoptosis and their potential significance in determining the prognosis of patients with non-early stage gastric carcinoma.

METHODS

Primary gastric tumor specimens from 225 patients were investigated by immunohistochemistry with anti-p27Kip1 and anti-Ki-67 antibodies, and their apoptotic indices were determined with the use of an Apop-Tag in situ detection kit.

RESULTS

The median p27Kip1 labeling index (LI) was 48.4%. There was a significant association between the p27 LIs and the apoptotic indices (Als). However, there was no association between the p27 LIs and the Ki-67 LIs. p27 LI was demonstrated to be one of the most significant and independent prognostic factors in multivariate analysis. Although AI was found to be prognostically significant in univariate analysis, it failed to retain an independent and significant value regarding overall survival in multivariate analysis.

CONCLUSIONS

Decreased expression of p27Kip1 and reduction of apoptotic potential were two of the most important factors in predicting a poor prognosis for patients with non-early stage gastric carcinoma. These findings support the hypothesis that decreased p27Kip1 expression, which may reflect a decreased rate of apoptosis, is closely related to the aggressiveness of gastric carcinoma. Therefore, the assessment of p27Kip1 expression and apoptotic potential may prove valuable in identifying patients with gastric carcinoma who are at high risk for recurrence and would benefit from adjuvant therapy.

摘要

背景

p27Kip1的表达和细胞凋亡与肿瘤侵袭性有关,并且已被证明是几种人类恶性肿瘤的预后预测指标。在本研究中,作者试图研究p27Kip1的表达和细胞凋亡及其在确定非早期胃癌患者预后方面的潜在意义。

方法

用抗p27Kip1和抗Ki-67抗体通过免疫组织化学法对225例患者的原发性胃肿瘤标本进行研究,并使用Apop-Tag原位检测试剂盒测定其凋亡指数。

结果

p27Kip1标记指数(LI)的中位数为48.4%。p27 LI与凋亡指数(AI)之间存在显著相关性。然而,p27 LI与Ki-67 LI之间没有相关性。在多变量分析中,p27 LI被证明是最重要的独立预后因素之一。虽然在单变量分析中发现AI具有预后意义,但在多变量分析中,它在总生存期方面未能保持独立且显著的价值。

结论

p27Kip1表达降低和凋亡潜能降低是预测非早期胃癌患者预后不良的两个最重要因素。这些发现支持以下假设:p27Kip1表达降低可能反映凋亡率降低,与胃癌的侵袭性密切相关。因此,评估p27Kip1表达和凋亡潜能可能有助于识别复发风险高且将从辅助治疗中获益的胃癌患者。

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