Leys Charles M, Nomura Sachiyo, LaFleur Bonnie J, Ferrone Soldano, Kaminishi Michio, Montgomery Elizabeth, Goldenring James R
Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232-2733, USA.
Surgery. 2007 Jan;141(1):41-50. doi: 10.1016/j.surg.2006.05.009. Epub 2006 Aug 14.
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 metaplasia and adenocarcinoma and clinical outcomes.
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.
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.
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.
在幽门螺杆菌诱导的胃化生和肿瘤形成的小鼠模型中，前胸腺素α和内质网蛋白57先前被确定为胃化生的标志物。在本文中，我们评估这些假定生物标志物在人类中的表达是否与胃化生、腺癌及临床结局相关。
八个组织芯片包含来自164例胃癌患者的749个石蜡包埋组织芯，采用辣根过氧化物酶免疫组织化学技术对前胸腺素α和内质网蛋白57进行染色。使用Ariol SL - 50自动图像分析系统对每个芯中染色细胞的比例进行定量。
与正常胃黏膜相比，前胸腺素α在癌组织和转移灶中染色的细胞核百分比显著更高。与正常胃黏膜和化生组织相比，内质网蛋白57在癌组织和转移灶中的染色显著减少。内质网蛋白57的表达也与肿瘤浸润深度增加和疾病晚期相关。Kaplan - Meier生存分析确定，内质网蛋白57表达处于最高四分位数的肿瘤在统计学上与术后生存期延长相关。Cox比例风险分析表明，内质网蛋白57表达的维持与术后生存期延长相关。
这些结果表明，虽然前胸腺素α在胃腺癌中过度表达，但它与生存期改变无关。相反，内质网蛋白57表达的缺失与更具侵袭性的疾病相关，可为胃癌患者提供有用的预后信息。
