Abstract 1058: Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: Analyses of clinopathological characteristics related with success

Autor: Min-Hee Ryu, Young-Soon Na, Young Soo Park, JW Lee, Chae-Won Lee, Jungmin Park, Yoon-Koo Kang, Jungeun Ma, Yangsoon Park
Rok vydání: 2019
Předmět:
Zdroj: Cancer Research. 79:1058-1058
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2019-1058
Popis: BACKGROUND: The gastrointestinal stromal tumor (GIST) has activating mutations in either KIT or platelet-derived growth factor receptor alpha (PDGFRa) gene, and tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib and regorafenib remain the mainstay of anti-GIST treatment. Patient-derived xenografts (PDXs) are useful preclinical models in cancer research, owing to their demonstration of more real tumor heterogeneity and complexity, compared with cell lines and cell line-based xenograft models. PDX models have been established using numerous tumor types, however, there are only a few PDX models of GIST because of its very low success rate. As we have been establishing PDXs from GIST patients since 2012, in this study, we report the established PDXs and the clinopathological characteristics related to the successful establishment of GIST PDXs. MATERIALS and METHODS: PDXs have been established in NOD-scid Il2rg-/- (NSG) mice by implanting GIST tumor fragments from 185 patients who underwent surgical resection prior to and after tyrosine kinase inhibitors from July, 2012 to July, 2017. The established PDXs passaged greater than F2 generation. Chi-square test and logistic regression were used for comparison. RESULTS: Of a total of 185 patients, 66 (35.7%) patients were TKI-naïve, 21 (11.4%) had residual disease after control with TKIs, and the remaining 98 (53.0%) showed disease progression after TKIs at the time of surgical resection. The success rate of establishment of GIST PDXs was 16.8% (31/185). In univariate analyses, a higher engraftment rate was observed for tumors derived from patients with disease progression after TKIs (TKI-naïve vs residual disease vs progressive disease; p100 mm; p10/50 HPFs; p CONCLUSION: Clinicopathologic factors such as disease progression after TKIs, larger tumor size, more mitotic count, higher Ki-67 index, higher cellularity or tumor necrosis were associated with higher success rate of PDX establishment. Especially, largest tumor size and Ki-67 index were independent factors for successful PDX engraftment. These findings will be helpful to establish PDX models more efficiently in GIST. Citation Format: Young-Soon Na, Min-Hee Ryu, Young Soo Park, Chae-Won Lee, Ju-Kyung Lee, Yangsoon Park, Jung Min Park, Jungeun Ma, Yoon-Koo Kang. Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: Analyses of clinopathological characteristics related with success [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1058.
Databáze: OpenAIRE
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