Tumor infiltrating neutrophils and gland formation predict overall survival and molecular subgroups in pancreatic ductal adenocarcinoma

Cancer Medicine

Andrew J. Mungall¹  Richard A. Moore¹  Marco A. Marra¹  Jessica Nelson¹  Steven J.M. Jones¹  Steve E. Kalloger²  Julia R. Naso³  David F. Schaeffer³  Hui‐li Wong⁴  Michael K.C. Lee⁴  Janessa Laskin⁴  James T. Topham⁵  Joanna M. Karasinska⁵  Daniel J. Renouf⁵ 

[1] Canada's Michael Smith Genome Sciences Centre Vancouver BC Canada;Department of Pathology and Laboratory Medicine University of British Columbia Vancouver BC Canada;Division of Anatomic Pathology Vancouver General Hospital Vancouver BC Canada;Division of Medical Oncology BC Cancer Vancouver BC Canada;Pancreas Centre BC Vancouver BC Canada;

关键词: molecular;    pancreatic neoplasms;    pathology;    pathology;    prognosis;   

DOI  :  10.1002/cam4.3695

来源: DOAJ

【 摘 要 】

ABSTRACT Background RNA‐sequencing‐based classifiers can stratify pancreatic ductal adenocarcinoma (PDAC) into prognostically significant subgroups but are not practical for use in clinical workflows. Here, we assess whether histomorphological features may be used as surrogate markers for predicting molecular subgroup and overall survival in PDAC. Methods Ninety‐six tissue samples from 50 patients with non‐resectable PDAC were scored for gland formation, stromal maturity, mucin, necrosis, and neutrophil infiltration. Prognostic PDAC gene expression classifiers were run on all tumors using whole transcriptome sequencing data from the POG trial (NCT02155621). Findings were validated using digital TCGA slides (n = 50). Survival analysis used multivariate Cox proportional‐hazards tests and log‐rank tests. Results The combination of low gland formation and low neutrophil infiltration was significantly associated with the poor prognosis PDAC molecular subgroup (basal‐like or squamous) and was an independent predictor of shorter overall survival, in both frozen section (n = 47) and formalin‐fixed paraffin‐embedded (n = 49) tissue samples from POG patients, and in the TCGA samples. This finding held true in the subgroup analysis of primary (n = 17) and metastatic samples (n = 79). The combination of high gland formation and high neutrophils had low sensitivity but high specificity for favorable prognosis subgroups. Conclusions The assessment of gland formation and neutrophil infiltration on routine histological sections can aid in prognostication and allow inferences to be made about molecular subtype, which may help guide patient management decisions and contribute to our understanding of heterogeneity in treatment response.

【 授权许可】

Unknown