Expression and prognostic significance of prothymosin-α and ERp57 in human gastric cancer
Expression and prognostic significance of prothymosin-α and ERp57 in human gastric cancer
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DOI：
10.1016/j.surg.2006.05.009
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发表时间：
2007-01-01
期刊：
影响因子：
3.8
通讯作者：
Goldenring, James R.
中科院分区：
文献类型：
--
作者：
Leys, Charles M.;Nomura, Sachiyo;Goldenring, James R.
目的。在幽门螺杆菌诱导的胃化生和瘤变小鼠模型中，胸腺肽原- α和ERp57被认为是胃化生的标志物。在本文中，我们评估了这些推测的生物标志物在人类中的表达是否与胃黑色素瘤和腺癌以及临床结果相关。采用辣根过氧化物酶免疫组化技术，对164例胃癌患者的749个石蜡包埋组织核进行了8个组织芯片的胸腺肽原- α和ERp57染色。采用Ariol SL-50自动图像分析系统定量测定每核染色细胞的比例。与正常胃粘膜相比，癌和转移灶中胸腺原酶- α染色的细胞核比例明显更高。与正常胃粘膜和化生组织相比，癌和转移灶的ERp57染色明显降低。ERp57的表达也与肿瘤侵袭深度和疾病晚期相关。Kaplan-Meier生存分析表明，ERp57四分位数表达最高的肿瘤在统计学上与较长的术后生存相关。Cox比例风险分析显示，维持ERp57的表达与较长的术后生存相关。这些结果表明，虽然胸腺蛋白酶原在胃腺癌中过度表达，但它与生存的改变无关。相反，ERp57表达的缺失与更具侵袭性的疾病相关，可以为胃癌患者提供有用的预后信息。
Purpose. Prothymosin-alpha and ERp57 were Previously identified as markers for gastric metaplasia in a mouse model of Helicobacter-induced gastric metaplasia and neoplasia. In this paper we assess whether the expression of these putative biomarkers in humans is correlated with gastric melaplasia and adenocarcinoma and clinical outcomes.Methods. Eight tissue microarrays, containing 749 paraffin-embedded tissue cores from 164 gastric cancer patients, were stained for prothymosin-alpha and ERp57 by horseradish peroxidase immunohistochemical techniques. The proportion of stained cells per core was quantitated using the Ariol SL-50 automated image analysis system.Results. Prothymosin-alpha stained a significantly higher percentage of nuclei in cancer and metastases compared with normal gastric mucosa. ERp57 staining was significantly decreased in cancer and metastases compared with both normal gastric mucosa and metaplasias. ERp57 expression also correlated with greater depth of tumor invasion and advanced stage of disease. Kaplan-Meier survival analysis determined that tumors with the highest quartile of ERp57 expression were statistically associated with longer postoperative survival. A Cox proportional hazard analysis showed that maintenance of ERp57 expression was associated with longer postoperative survival.Conclusions. These results suggest that although prothymosin-alpha is overexpressed in gastric adenocarcinoma, it is not associated with alterations in survival. In contrast, loss of ERp57 expression correlated with more aggressive disease and could provide useful prognostic information for gastric cancer patients.