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 (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Wang ZX; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Bowne WB; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Torjani A; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Swaminathan V; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Kavanagh TR; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Roadarmel A; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Sholevar CJ; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Cannaday S; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Gorgov E; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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 (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Jiang W; From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.; 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 Dec 01; Vol. 148 (12), pp. 1299-1309.
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
Externí odkaz:	Zobrazit plný text záznamu