Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

Autor:	Chao T; From the Department of Pathology and Genomic Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Chao, Wang, Peiper, Jiang)., Wang ZX; From the Department of Pathology and Genomic Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Chao, Wang, Peiper, Jiang)., Bowne WB; the Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)., Yudkoff CJ; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar)., Torjani A; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar)., Swaminathan V; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar)., Kavanagh TR; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar)., Roadarmel A; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar)., Sholevar CJ; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar)., Cannaday S; the Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)., Krampitz G; the Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)., Zhan T; the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Zhan)., Gorgov E; the Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)., Nevler A; the Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)., Lavu H; the Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)., Yeo CJ; the Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)., Peiper SC; From the Department of Pathology and Genomic Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Chao, Wang, Peiper, Jiang)., Jiang W; From the Department of Pathology and Genomic Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania(Chao, Wang, Peiper, Jiang).; the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang).
Jazyk:	angličtina
Zdroj:	Archives of pathology & laboratory medicine [Arch Pathol Lab Med] 2024 Mar 08. Date of Electronic Publication: 2024 Mar 08.
DOI:	10.5858/arpa.2023-0005-OA
Abstrakt:	Context.—: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. Objective.—: To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. Design.—: Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. Results.—: In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). Conclusions.—: PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies. Competing Interests: The authors have no relevant financial interest in the products or companies described in this article. (© 2024 College of American Pathologists.)
Databáze:	MEDLINE
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