Department of Pathology, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
Pancreas. 2013 Aug;42(6):1027-33. doi: 10.1097/MPA.0b013e31828804e7.
Pancreatic cancer is one of the most lethal malignancies; its poor prognosis is strongly associated with invasion and metastasis. Expression of S100A4 has been reported to correlate with poor prognosis in various cancers. We have investigated the role of S100A4 in pancreatic cancer tumorigenesis and its clinicopathologic significance.
Protein expression of S100A4 was examined by Western blot in pancreatic cancer cell lines and a human pancreatic ductal epithelium cell line, HPDE-6. Then the expressions of S100A4, TP53, and CD133 were examined immunohistochemically in resected specimens from 83 patients with pancreatic cancer to clarify their clinicopathologic significance. Survival analyses were performed using the Kaplan-Meier method and the Mantel-Cox method.
Forty-eight (58%) of 83 patients with pancreatic cancer positively expressed S100A4, and 50 (60%) and 29 (36%) patients positively expressed TP53 and CD133, respectively. S100A4 expression was significantly correlated with perineural invasion (P = 0.029) and invasion pattern (P = 0.001). Neither TP53 nor CD133 expression showed significant correlations with any other parameters.
Our present results suggest that S100A4 plays an important role in the invasiveness, particularly with perineural invasion and invasion pattern, of pancreatic cancer. Development of new strategies targeting S100A4 or its downstream effectors is warranted.
胰腺癌是最致命的恶性肿瘤之一;其预后不良与侵袭和转移密切相关。有报道称,S100A4 的表达与多种癌症的不良预后相关。我们研究了 S100A4 在胰腺癌发生发展中的作用及其与临床病理特征的关系。
采用 Western blot 检测 S100A4 在胰腺癌细胞系和人胰腺导管上皮细胞系 HPDE-6 中的蛋白表达。然后,采用免疫组织化学法检测 83 例胰腺癌患者切除标本中 S100A4、TP53 和 CD133 的表达,以明确其与临床病理特征的关系。采用 Kaplan-Meier 法和 Mantel-Cox 法进行生存分析。
83 例胰腺癌患者中,48 例(58%)表达 S100A4,50 例(60%)和 29 例(36%)患者表达 TP53 和 CD133。S100A4 的表达与神经周围侵犯(P=0.029)和浸润模式(P=0.001)显著相关。TP53 和 CD133 的表达均与其他参数无显著相关性。
本研究结果提示,S100A4 在外周神经侵犯和浸润模式等方面,对胰腺癌的侵袭性具有重要作用。针对 S100A4 或其下游效应物的新治疗策略值得进一步研究。