An Efficient Method for Cloning Gastrointestinal Stem Cells From Patients via Endoscopic Biopsies.
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ABSTRACT:
SUBMITTER: Duleba M
PROVIDER: S-EPMC6309951 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
An Efficient Method for Cloning Gastrointestinal Stem Cells From Patients via Endoscopic Biopsies.
Duleba Marcin M Qi Yutao Y Mahalingam Rajasekaran R Liew Audrey-Ann AA Neupane Rahul R Flynn Kevin K Rinaldi Fabrizio F Vincent Matthew M Crum Christopher P CP Ho Khek Yu KY Hou Jason K JK Hyams Jeffrey S JS Sylvester Francisco A FA McKeon Frank F Xian Wa W
Gastroenterology 20181006 1
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Project description:AimTo evaluate endoscopic ultrasound (EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients.MethodsAll patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase (2006-2011), routine fine-needle-aspiration (EUS-FNA) was performed. In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS-FNA and fine-needle-biopsy-sampling (EUS-FNB) for all lesions. c-KIT- and DOG-1-immunostaining was attempted in all samples and a manual count of the Ki-67-index was performed. FNB-sampled tissue and the resected specimens were subjected to Sanger sequencing of the KIT and platelet-derived growth factor alpha (PDGFRA) genes.ResultsIn all, 64 unique patients with GIST were included, and of these, 38 were subjected to pretreatment dual sampling. EUS-FNB had a higher diagnostic sensitivity when compared head-to-head with EUS-FNA (98% vs 58%, P < 0.001) and was more adequate for Ki-67-indexing (Ki-67EUS) (92% vs 40%, P < 0.001). Sequencing of EUS-biopsies was successful in 43/44 (98%) patients, and the mutation profiles (KIT-mutation 73%, PDGFRA-mutation 18%, wild-type 7%) were fully congruent with those detected in the corresponding resected specimens. In imatinib-naïve patients, the Ki-67EUS was comparable with the Ki-67-index in the corresponding surgical specimens (Ki-67SURG) (2.7% vs 2.9%, P = 0.68). In patients treated with neoadjuvant imatinib who also carried mutations indicating sensitivity, the Ki-67EUS was higher than the Ki-67SURG (2.5% vs 0.2%, P = 0.005), with a significant reduction in the Ki-67-index of -91.5% (95%CI: -82.4 to -96.0, P = 0.005).ConclusionEUS-guided biopsy sampling is accurate for the pretreatment diagnosis and characterization of GISTs and allows the prediction and evaluation of tumor response to neoadjuvant imatinib therapy.
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