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

Autor: Naso JR; Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Topham JT; Pancreas Centre BC, Vancouver, BC, Canada., Karasinska JM; Pancreas Centre BC, Vancouver, BC, Canada., Lee MKC; Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada., Kalloger SE; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.; Pancreas Centre BC, Vancouver, BC, Canada., Wong HL; Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada., Nelson J; Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada., Moore RA; Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada., Mungall AJ; Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada., Jones SJM; Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada., Laskin J; Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada., Marra MA; Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada., Renouf DJ; Pancreas Centre BC, Vancouver, BC, Canada.; Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada., Schaeffer DF; Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.; Pancreas Centre BC, Vancouver, BC, Canada.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2021 Feb; Vol. 10 (3), pp. 1155-1165. Date of Electronic Publication: 2020 Dec 28.
DOI: 10.1002/cam4.3695
Abstrakt: 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.
(© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje