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新辅助治疗后病理完全缓解的直肠癌患者中癌胚抗原、上皮细胞黏附分子、αvβ6和尿激酶型纤溶酶原激活物受体的表达

CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy.

作者信息

Linders Daan, Deken Marion, van der Valk Maxime, Tummers Willemieke, Bhairosingh Shadhvi, Schaap Dennis, van Lijnschoten Gesina, Zonoobi Elham, Kuppen Peter, van de Velde Cornelis, Vahrmeijer Alexander, Farina Sarasqueta Arantza, Sier Cornelis, Hilling Denise

机构信息

Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Department of Surgery, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands.

出版信息

Diagnostics (Basel). 2021 Mar 14;11(3):516. doi: 10.3390/diagnostics11030516.

Abstract

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed ( < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

摘要

新辅助治疗后获得完全缓解的直肠癌患者可采用观察等待策略进行监测。然而,复发率表明,识别病理完全缓解(pCR)患者仍然具有挑战性。靶向近红外荧光内镜检查是一种改善疗效评估的潜在工具。有前景的肿瘤靶点包括癌胚抗原(CEA)、上皮细胞粘附分子(EpCAM)、整合素αvβ6和尿激酶型纤溶酶原激活物受体(uPAR)。为了研究这些靶点的适用性,我们通过免疫组织化学分析了蛋白质表达,并通过总免疫染色评分(TIS)对pCR直肠癌患者组织中的这些蛋白进行了定量。在诊断性活检中,CEA、EpCAM、αvβ6和uPAR的表达分别在100%、100%、33%和46%的病例中较高(TIS>6)。与相应的肿瘤床相比,诊断性活检中的CEA和EpCAM表达显著更高(<0.01)。在肿瘤床中,CEA、EpCAM、αvβ6和uPAR的表达分别在93%、95%、85%和62.5%的病例中较低(TIS<6)。免疫组织化学评估表明,CEA和EpCAM可能是新辅助治疗后疗效评估的合适靶点,因为在超过90%的pCR患者中,这些靶点在原发性肿瘤床中的表达与诊断性活检及相邻的原有直肠黏膜相比更低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b357/8002064/db11c4426967/diagnostics-11-00516-g001.jpg

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