Elf Anna-Karin, Johanson Viktor, Marin Ida, Bergström Anders, Nilsson Ola, Svensson Johanna, Wängberg Bo, Bernhardt Peter, Elias Erik
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
Department of Endocrine Surgery, Sahlgrenska University Hospital, 405 30 Gothenburg, Sweden.
Cancers (Basel). 2021 Apr 23;13(9):2035. doi: 10.3390/cancers13092035.
(1) Purpose: Small intestinal neuroendocrine tumors (SI-NETs) often present with distant metastases at diagnosis. Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a systemic treatment that increases overall survival (OS) in SI-NET patients with stage IV disease. However, the treatment response after PRRT, which targets somatostatin receptor 2 (SSTR2), is variable and predictive factors have not been established. This exploratory study aims to evaluate if SSTR2 expression in SI-NETs could be used to predict OS after PRRT treatment. (2) Methods: Using a previously constructed Tissue Micro Array (TMA) we identified tissue samples from 42 patients that had received PRRT treatment during 2006-2017 at Sahlgrenska University hospital. Immunohistochemical expression of SSTR2, Ki-67 and neuroendocrine markers synaptophysin and Chromogranin A (CgA) were assessed. A retrospective estimation of Lu-DOTATATE uptake in 33 patients was performed. Data regarding OS and non-surgical treatment after PRRT were collected. Another subgroup of 34 patients with paired samples from 3 tumor sites (primary tumor, lymph node and liver metastases) was identified in the TMA. The SSTR2 expression was assessed in corresponding tissue samples ( = 102). (3) Results: The patients were grouped into Low SSTR2 or High SSTR2 groups based upon on levels of SSTR2 expression. There was no significant difference in Lu-DOTATATE uptake between the groups. The patients in the Low SSTR2 group had significantly longer OS after PRRT than the patients in the High SSTR2 group ( = 0.049). PRRT treated patients with low SSTR2 expression received less additional treatment compared with patients with high SSTR2 expression. SSTR2 expression did not vary between tumor sites but correlated within patients. (4) Conclusion: The results from the present study suggest that retrospective evaluation of SSTR2 expression in resected tumors cannot be used to predict OS after PRRT.
（1）目的：小肠神经内分泌肿瘤（SI-NETs）在诊断时常常已有远处转移。用放射性标记的生长抑素类似物进行肽受体放射性核素治疗（PRRT）是一种全身治疗方法，可提高IV期SI-NET患者的总生存期（OS）。然而，以生长抑素受体2（SSTR2）为靶点的PRRT治疗反应存在差异，且尚未确立预测因素。这项探索性研究旨在评估SI-NETs中SSTR2表达是否可用于预测PRRT治疗后的OS。（2）方法：利用先前构建的组织微阵列（TMA），我们从2006年至2017年期间在萨尔格伦斯卡大学医院接受PRRT治疗的42例患者中识别出组织样本。评估SSTR2、Ki-67以及神经内分泌标志物突触素和嗜铬粒蛋白A（CgA）的免疫组化表达。对33例患者进行了镥-奥曲肽摄取的回顾性评估。收集PRRT治疗后关于OS和非手术治疗的数据。在TMA中识别出另一组34例患者，其有来自3个肿瘤部位（原发肿瘤、淋巴结和肝转移灶）的配对样本。在相应的组织样本（n = 102）中评估SSTR2表达。（3）结果：根据SSTR2表达水平将患者分为低SSTR2组或高SSTR2组。两组之间镥-奥曲肽摄取无显著差异。低SSTR2组患者PRRT治疗后的OS显著长于高SSTR2组患者（P = 0.049）。与高SSTR2表达患者相比，低SSTR2表达的PRRT治疗患者接受的额外治疗较少。SSTR2表达在肿瘤部位之间无差异，但在患者体内具有相关性。（4）结论：本研究结果表明，对切除肿瘤中SSTR2表达的回顾性评估不能用于预测PRRT治疗后的OS。
