Vimalachandran Dale, Greenhalf William, Thompson Christopher, Lüttges Jutta, Prime Wendy, Campbell Fiona, Dodson Andrew, Watson Richard, Crnogorac-Jurcevic Tatjana, Lemoine Nicholas, Neoptolemos John, Costello Eithne
Division of Surgery and Oncology, Department of Pathology, University of Liverpool, Liverpool, Merseyside, UK.
Cancer Res. 2005 Apr 15;65(8):3218-25. doi: 10.1158/0008-5472.CAN-04-4311.
Recent studies have reported elevated levels of S100A6 in pancreatic ductal adenocarcinoma cells. Here, we describe a detailed analysis of S100A6 expression in benign (n = 32), malignant (n = 60), and premalignant pancreatic ductal cells [96 pancreatic intraepithelial neoplasias (PanIN) from 46 patients]. S100A6 staining was more intense in malignant cells than in benign cells (P = 0.0001). In malignant cells, staining was higher in the nucleus than in the cytoplasm (P = 0.003). Univariate analysis revealed a significant decrease in survival time for patients with high levels of nuclear (P = 0.01) but not cytoplasmic (P = 0.20) S100A6. No evidence was found for an association between nuclear S100A6 expression and other variables, including gender, age at surgery, tumor size or grade, nodal metastases, resection margin, vascular invasion, perineural invasion, p53 or Smad4 levels (both linked to survival in previous studies), or the p65 subunit of nuclear factor-kappaB (a potential regulator of S100A6). Although nodal metastases and resection margin involvement were also associated with poor survival (P = 0.06 in both cases), multivariate analysis suggests that nuclear S100A6 is a significant independent indicator of survival (P = 0.003). Whereas PanIN 1a lesions showed a general absence of S100A6 staining, there was a progressive increase in the proportion of positively stained PanINs with increasing PanIN grade. In particular, we observed an increase in the frequency and intensity of nuclear staining. Our results suggest that up-regulation of S100A6 is an early event in pancreatic cancer development and that elevated levels of nuclear S100A6 may affect clinical outcome.
近期研究报道，胰腺导管腺癌细胞中S100A6水平升高。在此，我们详细分析了S100A6在良性（n = 32）、恶性（n = 60）和癌前胰腺导管细胞[来自46例患者的96个胰腺上皮内瘤变（PanIN）]中的表达情况。S100A6染色在恶性细胞中比在良性细胞中更强烈（P = 0.0001）。在恶性细胞中，细胞核中的染色高于细胞质中的染色（P = 0.003）。单因素分析显示，核S100A6水平高的患者生存时间显著缩短（P = 0.01），而细胞质S100A6水平高的患者生存时间无显著缩短（P = 0.20）。未发现核S100A6表达与其他变量之间存在关联，这些变量包括性别、手术年龄、肿瘤大小或分级、淋巴结转移、切缘、血管侵犯、神经周围侵犯、p53或Smad4水平（在先前研究中均与生存相关），或核因子κB的p65亚基（S100A6的潜在调节因子）。尽管淋巴结转移和切缘受累也与生存不良相关（两者P值均为0.06），但多因素分析表明核S100A6是生存的显著独立指标（P = 0.003）。虽然PanIN 1a病变通常无S100A6染色，但随着PanIN分级增加，阳性染色的PanIN比例逐渐升高。特别是，我们观察到核染色的频率和强度增加。我们的结果表明，S100A6上调是胰腺癌发生发展的早期事件，核S100A6水平升高可能影响临床结局。
