1. Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma
- Author
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Chao, Timothy, Wang, Zi-Xuan, Bowne, Wilbur B., Yudkoff, Clifford J., Torjani, Ava, Swaminathan, Vishal, Kavanagh, Taylor R., Roadarmel, Austin, Sholevar, Cyrus J., Cannaday, Shawnna, Krampitz, Geoffrey, Zhan, Tingting, Gorgov, Eliyahu, Nevler, Avinoam, Lavu, Harish, Yeo, Charles J., Peiper, Stephen C., and Jiang, Wei
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Medical research ,Medicine, Experimental ,Adenocarcinoma -- Physiological aspects -- Genetic aspects -- Patient outcomes ,Morphology -- Health aspects ,Allelomorphism -- Health aspects ,Pancreatic cancer -- Genetic aspects -- Physiological aspects -- Patient outcomes ,Health ,Physiological aspects ,Genetic aspects ,Patient outcomes ,Health aspects - Abstract
* 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 [greater than or equal to]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. (Arch Pathol Lab Med. 2024;148:1299-1309; doi: 10.5858/arpa.2023-0005-OA), Pancreatic cancer, the majority of which consists of pancreatic ductal adenocarcinomas (PDACs), is projected to become the second leading cause of cancer-related deaths by 2030. (1) Surgical resectability is the [...]
- Published
- 2024
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