The prognostic significance of p21 and Her-2 gene expression and mutation/polymorphism in patients with gastric adenocarcinoma

The prognostic significance of p21 and Her-2 gene expression and mutation/polymorphism in patients with gastric adenocarcinoma
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DOI:
10.1007/s12032-012-0357-y
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发表时间:
2013-03-01
期刊:
影响因子:
3.4
通讯作者:
Karagol, Hakan
Karagol, Hakan
中科院分区:
医学4区
文献类型:
--
作者:
Ozen, Alaattin;Kocak, Zafer;Karagol, Hakan

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分析基因表达状态和遗传多态性是识别新的组织病理预后因素的方法。在胃癌患者中,一些细胞周期调节因子p53、p21、p27和Her-2癌基因被认为是影响预后的因素。我们旨在探讨p21和Her-2基因在胃癌患者中的表达、突变/多态性及其与组织病理因素和预后的关系。本研究分析了2000年1月至2008年12月44例局部晚期胃癌患者。临床病理参数、p21的表达和突变/多态性以及Her-2结果用于预测无病生存期和总生存期。44例肿瘤中p21和Her-2阳性表达率分别为61.4% (n = 27)和9.1% (n = 4)。p21基因突变占20% (n = 11), Her-2基因多态性占2.3% (n = 1, II型)。p21的阴性表达与弥漫性和未分化型组织学、全胃受累和血管/神经浸润阳性相关。p21阴性表达患者的中位生存率显著低于p21阳性表达患者(17个月vs. 27个月,p = 0.01, cox回归)。P21突变在弥漫性(p = 0.03)和非分化型(p = 0.02)患者中明显更高。组织病理学参数与Her-2基因多态性/表达无统计学意义。p21的阴性表达与疾病生存相关,可能是切除胃癌患者接受辅助化疗的不良预后因素。
Analyses of gene expression status and genetic polymorphisms are methods to identify novel histopathological prognostic factors. In patients with gastric cancer, some cell cycle regulators p53, p21, p27 and Her-2 oncogene have been proposed as prognostic factors. We aimed to investigate the expression and mutation/polymorphism of p21 and Her-2 and also relationship between that genes status and histopathological factors and prognosis in patients with gastric cancer. Forty-four patients with locally advanced gastric cancer were analyzed in this study from January 2000 to December 2008. Clinicopathological parameters, expression and mutation/polymorphism of p21 and Her-2 results were used to predict disease-free survival and overall survival. The positive expression of p21 and Her-2 was observed in 61.4 % (n = 27) and 9.1 % (n = 4) of all 44 tumors, respectively. p21 gene mutation and Her-2 gene polymorphism were detected in 20 % (n = 11) and 2.3 % (n = 1, II phenotype) of cases, respectively. The negative expression of p21 was correlated significantly with diffuse and undifferential type histologies, whole gastric involvement and positive vascular/neural invasion. The median survival rate of patients with negative expression was significantly poorer than that of patients with positive expression of p21 (17 vs. 27 months, p = 0.01, cox regression). p21 mutation was significantly higher in patients with diffuse (p = 0.03) and undifferential (p = 0.02) type histologies. There was no statistically significant association between histopathological parameters and Her-2 gene polymorphism/expression. The negative expression of p21 correlates with disease survival and may be a poor prognostic factor in patients with resected gastric cancer treated with adjuvant chemotherapy.