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

Authors

• Timothy Chao
• Zi-Xuan Wang
• Wilbur B Bowne
• Clifford J Yudkoff
• Ava Torjani
• Vishal Swaminathan
• Taylor R Kavanagh
• Austin Roadarmel
• Cyrus J Sholevar
• Shawnna Cannaday
• Geoffrey Krampitz
• Tingting Zhan
• Eliyahu Gorgov
• Avinoam Nevler
• Harish Lavu
• Charles J Yeo
• Stephen C Peiper
• Wei Jiang

Publication/Presentation Date

12-1-2024

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 ≥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.

Volume

148

Issue

12

First Page

1299

Last Page

1309

ISSN

1543-2165

Published In/Presented At

Chao, T., Wang, Z. X., Bowne, W. B., Yudkoff, C. J., Torjani, A., Swaminathan, V., Kavanagh, T. R., Roadarmel, A., Sholevar, C. J., Cannaday, S., Krampitz, G., Zhan, T., Gorgov, E., Nevler, A., Lavu, H., Yeo, C. J., Peiper, S. C., & Jiang, W. (2024). Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma. Archives of pathology & laboratory medicine, 148(12), 1299–1309. https://doi.org/10.5858/arpa.2023-0005-OA

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

38452805

Department(s)

Administration and Leadership

Document Type

Article