Sinn M, Denkert C, Striefler J K, Pelzer U, Stieler J M, Bahra M, Lohneis P, Dörken B, Oettle H, Riess H, Sinn B V
Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
Charité-Universitätsmedizin Berlin, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
Br J Cancer. 2014 Nov 11;111(10):1917-23. doi: 10.1038/bjc.2014.495. Epub 2014 Oct 14.
Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin (α-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of α-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients.
CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of α-SMA expression and stromal density impact on patient outcome.
High α-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, α-SMA and stromal density expression were independently predictive factors for survival.
Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy.
先前对胰腺癌的研究表明，α-平滑肌肌动蛋白（α-SMA）表达和肿瘤周围基质中的基质密度具有预后作用。本研究的目的是进一步验证与未接受治疗的患者相比，α-SMA表达和基质密度对接受吉西他滨辅助治疗的可切除胰腺癌患者的影响。
CONKO-001是一项前瞻性随机III期研究，旨在研究吉西他滨辅助治疗与观察相比的作用。162例患者的组织样本可用于组织微阵列上的免疫组织化学，以评估α-SMA表达和基质密度对患者预后的影响。
肿瘤基质中高α-SMA表达与较差的患者预后相关（无病生存期：P = 0.05，总生存期：P = 0.047）。在整个研究人群中，致密的基质反应与无病生存期（DFS）和总生存期（OS）的改善相关（DFS：P = 0.001，OS：P = 0.001）。这种积极的预后影响仅限于未接受辅助治疗的患者（DFS：P <0.001，OS：P <0.001）。在多变量分析中，α-SMA和基质密度表达是生存的独立预测因素。
我们的数据证实了根治性切除术后胰腺癌患者中高α-SMA表达的负面预后影响。与先前的研究相反，我们发现致密基质具有积极的预后影响。这种显著影响仅限于未接受辅助治疗的患者。
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