Journal
CANCER MEDICINE
Volume 10, Issue 3, Pages 1155-1165Publisher
WILEY
DOI: 10.1002/cam4.3695
Keywords
molecular; pancreatic neoplasms; pathology; pathology; prognosis
Categories
Funding
- Pancreas Centre BC
- University of British Columbia Department of Pathology Residency Training Program
- BC Cancer Foundation
- Genome BC [B20POG]
- Pancreatic Cancer Canada
- Terry Fox Research Institute [1078]
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This study assessed whether histomorphological features can be used as surrogate markers for predicting molecular subgroups and overall survival in PDAC. The combination of low gland formation and low neutrophil infiltration was significantly associated with poor prognosis PDAC subgroups and independently predicted shorter overall survival.
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.
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