Laboratory of Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
Eur J Cancer. 2010 Dec;46(18):3393-9. doi: 10.1016/j.ejca.2010.07.024. Epub 2010 Aug 17.
The high mortality rate and minimal progress made in the treatment of pancreatic cancer over the last few decades, warrant an alternative approach. Treatment protocols should be individualised to the patient guided by prognostic markers. A particularly interesting target would be the architectural transcription factor high mobility group A1 (HMGA1), that is low or undetectable in normal tissue, induced during neoplastic transformation and consequently often exceptionally high in cancer. The aim of the current study was therefore to determine the differential expression of HMGA1 in pancreatic head and periampullary cancer and investigate its relation with outcome. HMGA1 expression was determined by immunohistochemistry on original paraffin embedded tissue from 99 pancreatic head- and 112 periampullary cancers (with R0). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS) and conventional prognostic factors. HMGA1 was expressed in 47% and 26% of pancreatic head- and periampullary cancer, respectively and associated with poor RFS, CSS and OS in periampullary cancer. CSS 5years following surgery was 25% and 44% for patients with tumours which were positive or negative for HMGA1 protein, respectively. HMGA1 expression was not associated with survival in pancreatic head cancer. In conclusion HMGA1 was identified as an independent prognostic marker predicting poor outcome in periampullary cancer. Although expressed to a higher extent as compared to periampullary cancer, HMGA1 was not associated with survival in pancreatic head cancer.
在过去几十年中,胰腺癌的高死亡率和治疗进展甚微,这需要一种替代方法。治疗方案应根据预后标志物个体化制定。一个特别有趣的靶点是结构转录因子高迁移率族蛋白 A1(HMGA1),它在正常组织中低或不可检测,在肿瘤转化过程中诱导产生,因此在癌症中通常异常高。因此,目前的研究旨在确定 HMGA1 在胰头和壶腹周围癌中的差异表达,并研究其与预后的关系。通过对 99 例胰头癌和 112 例壶腹周围癌(RO )的原始石蜡包埋组织进行免疫组织化学检测,确定 HMGA1 的表达。研究 HMGA1 表达与无复发生存(RFS)、癌症特异性(CSS)和总生存(OS)以及传统预后因素的关系。HMGA1 在胰头癌和壶腹周围癌中的表达率分别为 47%和 26%,与壶腹周围癌的 RFS、CSS 和 OS 不良相关。手术后 5 年 CSS 分别为 HMGA1 蛋白阳性和阴性患者的 25%和 44%。HMGA1 表达与胰头癌的生存无关。总之,HMGA1 被确定为预测壶腹周围癌不良预后的独立预后标志物。尽管 HMGA1 的表达程度高于壶腹周围癌,但与胰头癌的生存无关。