Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: analysis of clinicopathological characteristics related to engraftment success

Autor: Yangsoon Park, Jungeun Ma, Yoon-Koo Kang, Young Soo Park, Young Soon Na, Jungmin Park, Chae-Won Lee, Min Hee Ryu, Ju Kyung Lee
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
ISSN: 2045-2322
Popis: 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-PrkdcscidIL2rgtm1Wjl/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.
Databáze: OpenAIRE
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