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
{"title":"突变 KRAS 等位基因与胰腺导管腺癌形态学和临床结果的关系","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","doi":"10.5858/arpa.2023-0005-OA","DOIUrl":null,"url":null,"abstract":"<p><strong>Context.—: </strong>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.</p><p><strong>Objective.—: </strong>To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles.</p><p><strong>Design.—: </strong>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.</p><p><strong>Results.—: </strong>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).</p><p><strong>Conclusions.—: </strong>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.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"doi\":\"10.5858/arpa.2023-0005-OA\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context.—: </strong>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.</p><p><strong>Objective.—: </strong>To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles.</p><p><strong>Design.—: </strong>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.</p><p><strong>Results.—: </strong>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).</p><p><strong>Conclusions.—: </strong>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.</p>\",\"PeriodicalId\":93883,\"journal\":{\"name\":\"Archives of pathology & laboratory medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-03-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of pathology & laboratory medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5858/arpa.2023-0005-OA\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of pathology & laboratory medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5858/arpa.2023-0005-OA","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.
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.