Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sci Rep. 2020 May 14;10(1):7996. doi: 10.1038/s41598-020-64552-w.
Patient-derived xenografts (PDXs) can represent the heterogeneity and histological characteristics of tumors and are thus useful for testing the efficacy of anti-cancer drugs; however, PDXs are difficult to generate, especially for gastrointestinal stromal tumor (GIST). We analyzed the clinicopathologic factors associated with the successful establishment of GIST PDX in NOD.Cg-Prkdc IL2rg/SzJ mice. We used 185 GIST tumor fragments from patients who underwent surgical resection prior to (n = 66; 35.7%) and after treatment (n = 119; 64.3%) with tyrosine kinase inhibitors. The overall success rate of PDX establishment was 17%; in univariate analysis, engraftment success was associated with after TKI treatment, larger tumor size, higher mitotic count, higher Ki-67 index, higher cellularity, presence of tumor necrosis, primary mutations in KIT exon 11, and originating from metastatic lesions. In multivariate analysis, higher Ki-67 index, after TKI treatment, and larger tumor size were independent factors for engraftment success. Immunohistochemistry in representative samples further corroborated the above results. These results will be useful in the establishment of PDX models from GISTs.
患者来源异种移植物（PDX）可以代表肿瘤的异质性和组织学特征，因此可用于测试抗癌药物的疗效；然而，PDX 的生成较为困难，尤其是胃肠道间质瘤（GIST）。我们分析了与 NOD.Cg-Prkdc IL2rg/SzJ 小鼠中 GIST PDX 成功建立相关的临床病理因素。我们使用了 185 个来自接受酪氨酸激酶抑制剂（n=66；35.7%）治疗前和（n=119；64.3%）治疗后的 GIST 肿瘤患者的肿瘤碎片。PDX 建立的总体成功率为 17%；在单因素分析中，植入成功与 TKI 治疗后、更大的肿瘤大小、更高的有丝分裂计数、更高的 Ki-67 指数、更高的细胞密度、肿瘤坏死的存在、KIT 外显子 11 的原发性突变以及转移性病变有关。在多因素分析中，更高的 Ki-67 指数、TKI 治疗后和更大的肿瘤大小是植入成功的独立因素。代表性样本的免疫组织化学进一步证实了上述结果。这些结果将有助于 GIST 患者 PDX 模型的建立。
