α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study.
α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study.
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DOI：
10.1038/bjc.2014.495
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发表时间：
2014-11-11
影响因子：
8.8
通讯作者：
Sinn, B. V.
中科院分区：
文献类型：
--
作者：
Sinn, M.;Denkert, C.;Striefler, J. K.;Pelzer, U.;Stieler, J. M.;Bahra, M.;Lohneis, P.;Doerken, B.;Oettle, H.;Riess, H.;Sinn, B. V.
先前的胰腺癌研究表明，α-平滑肌肌动蛋白（α-SMA）表达和肿瘤周围间质中的间质密度具有预后作用。本研究的目的是进一步验证与未经治疗的患者相比，接受吉西他滨辅助治疗的可切除胰腺癌患者中α-SMA表达和基质密度的影响。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治疗相比的作用。162例患者的组织样本可用于组织微阵列的免疫组织化学，以评价α-SMA表达和基质密度对患者结局的影响。肿瘤间质中α-SMA高表达与患者结局较差相关（DFS：P=0.05，OS：P=0.047）。在整个研究人群中，致密间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）。多变量分析显示，α-SMA和基质密度表达是生存期的独立预测因素。我们的数据证实了α-SMA高表达对胰腺癌患者在根治性切除术后的预后有负面影响。与以前的研究相反，我们发现致密间质对预后有积极影响。这种显著影响仅限于未接受辅助治疗的患者。
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.
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影响因子：
4
作者：
Wilson JS;Pirola RC;Apte MV
通讯作者：
Apte MV
针对胰腺癌肿瘤相互作用的新型治疗策略。
影响因子：
4
作者：
Hamada S;Masamune A;Shimosegawa T
通讯作者：
Shimosegawa T
影响因子：
45.3
作者：
Infante, Jeffrey R.;Matsubayashi, Hiroyuki;Goggins, Michael
通讯作者：
Goggins, Michael
影响因子：
2.9
作者：
Fujita, Hayato;Ohuchida, Kenoki;Tanaka, Masao
通讯作者：
Tanaka, Masao
影响因子：
3.6
作者：
Lunevicius, R;Nakanishi, H;Yasui, K
通讯作者：
Yasui, K