Vay Christian, Babaei Shahrooz, Safi Sami-Alexander, Dizdar Levent, Rehders Alexander, Haeberle Lena, Roderburg Christoph, Loosen Sven H, Esposito Irene, Knoefel Wolfram T, Krieg Andreas
Department of Surgery (A), University Hospital Duesseldorf, Heinrich-Heine-University, Moorenstrasse 5, 40225 Duesseldorf, Germany.
Institute of Pathology, University Hospital Duesseldorf, Heinrich-Heine-University, Moorenstrasse 5, 40225 Duesseldorf, Germany.
Cancers (Basel). 2022 Jul 18;14(14):3494. doi: 10.3390/cancers14143494.
Background: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor. Thus, novel therapeutic concepts focus on the development of targeted therapies. In this context, inhibitor of apoptosis protein (IAP) survivin is regarded as a promising oncotherapeutic target. However, its expression and prognostic value in different tumour compartments of PDAC have not been studied. Methods: Immunohistochemical analysis of survivin in different PDAC tumour compartments from 236 consecutive patients was correlated with clinicopathological variables and survival. Results: In comparison to healthy pancreatic tissue high nuclear (p < 0.001) and high cytoplasmic (p < 0.01) survivin expression became evident in the tumour centre, along the invasion front and in lymph node metastases. Cytoplasmic overexpression of survivin in tumour centres was related to the presence of distant metastasis (p = 0.016) and UICC III/IV stages (p = 0.009), while high cytoplasmic expression at the invasion front grouped with venous infiltration (p = 0.022). Increased nuclear survivin along the invasion front correlated with perineural invasion (p = 0.035). High nuclear survivin in tumour centres represented an independent prognostic factor for overall survival of pancreatic tail carcinomas (HR 13.5 95%CI (1.4−129.7)) and correlated with a limited disease-free survival in PDAC (HR 1.80 95%CI (1.04−3.12)). Conclusion: Survivin is associated with advanced disease stages and poor prognosis. Therefore, survivin will help to identify patients with aggressive tumour phenotypes that could benefit from the inclusion in clinical trials incorporating survivin inhibitors in PDAC.
胰腺导管腺癌（PDAC）手术后的生存率仍然很低。因此，新的治疗理念聚焦于靶向治疗的开发。在这种背景下，凋亡抑制蛋白（IAP）survivin被视为一个有前景的肿瘤治疗靶点。然而，其在PDAC不同肿瘤区域的表达及预后价值尚未得到研究。方法：对236例连续患者的不同PDAC肿瘤区域进行survivin免疫组化分析，并与临床病理变量及生存率相关联。结果：与健康胰腺组织相比，肿瘤中心、浸润前沿及淋巴结转移灶中survivin高核表达（p < 0.001）和高胞质表达（p < 0.01）明显。肿瘤中心survivin胞质过表达与远处转移（p = 0.016）及UICC III/IV期（p = 0.009）有关，而浸润前沿高胞质表达与静脉浸润相关（p = 0.022）。浸润前沿核survivin增加与神经周围浸润相关（p = 0.035）。肿瘤中心高核survivin是胰尾癌总生存的独立预后因素（HR 13.5，95%CI（1.4−129.7）），并与PDAC有限的无病生存期相关（HR 1.80，95%CI（1.04−3.12））。结论：Survivin与疾病晚期及不良预后相关。因此，survivin将有助于识别具有侵袭性肿瘤表型的患者，这些患者可能受益于纳入含survivin抑制剂的PDAC临床试验。
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