Routine Molecular Profiling in Both Resectable and Unresectable Pancreatic Adenocarcinoma: Relevance of Cytologic Samples.

Autor:	Redegalli M; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Grassini G; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Magliacane G; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Pecciarini L; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Schiavo Lena M; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Smart CE; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Johnston RL; Unit of Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Waddell N; Unit of Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Maestro R; Unit of Oncogenetics and Functional Oncogenomics, Centro di Riferimento Oncologico Aviano, National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy., Macchini M; Department of Medical Oncology, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Orsi G; Department of Medical Oncology, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Petrone MC; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Rossi G; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Balzano G; Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Falconi M; Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Arcidiacono PG; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Reni M; Department of Medical Oncology, Pancreas Translational and Clinical Research Centre, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Doglioni C; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Cangi MG; Pathology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy. Electronic address: cangi.mariagiulia@hsr.it.
Jazyk:	angličtina
Zdroj:	Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [Clin Gastroenterol Hepatol] 2023 Oct; Vol. 21 (11), pp. 2825-2833. Date of Electronic Publication: 2022 Oct 22.
DOI:	10.1016/j.cgh.2022.10.014
Abstrakt:	Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease, for which it is crucial to promptly detect actionable and prognostic alterations to drive specific therapeutic decisions, regardless of tumor resectability status. Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is of key importance for PDAC diagnosis and can contribute significantly to tumor molecular profiling. Methods: Comprehensive genomic profile by targeted next-generation sequencing (NGS) was performed on 2 independent PDAC patient cohorts. Cohort 1 consisted of 77 patients with resectable PDAC for whom the histologic sample at the time of resection was available; for 56 patients cytologic specimens at the time of diagnosis also were obtained by EUS-FNA. Cohort 2 consisted of 20 patients with unresectable PDAC, for whom only the EUS-FNA cytologic sample was available. Results: In cohort 1, a complete concordant mutational profile between the cytologic sample at diagnosis and the corresponding histologic specimen after surgery was observed in 88% of the cases, proving the ability to detect potential clinically relevant alterations in cytologic samples by NGS analysis. Notably, clinically actionable mutations were identified in 20% of patients. In cohort 2, comprehensive mutational profiling was obtained successfully for all samples. Consistent with the findings of cohort 1, KRAS, TP53, CDKN2A, and SMAD4 were the most altered genes. Most importantly, 15% of the patients harbored actionable mutations. Conclusions: Our findings show the feasibility of an NGS approach using both surgical specimens and cytologic samples. The model proposed in this study can be included successfully in the clinical setting for comprehensive molecular profiling of all PDAC patients irrespective of their surgical eligibility. (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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