Synaptophysin expression in
(V600E)BRAF
Colorectal cancer
Immunohistochemistry
Neuroendocrine
Prognostic markers
Synaptophysin
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
14
10
2020
revised:
29
12
2020
accepted:
10
01
2021
pubmed:
20
2
2021
medline:
29
9
2021
entrez:
19
2
2021
Statut:
ppublish
Résumé
Neuroendocrine differentiation has been extensively associated with worse prognosis and to mechanisms of therapy resistance in several epithelial cancers. A high prevalence of neuroendocrine differentiation was recently described in We assessed synaptophysin immunohistochemical expression in a multi-institutional series of 159 BRAFmt mCRCs with matched clinical and pathological information. Tumours were dichotomized as synaptophysin high and low. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier and log-rank tests. Thirty-five tumours (22.0%) showed any level of positivity for synaptophysin, and 18 (11.3%) were characterized by positivity in at least 20% of tumour cells. Four cases resulted 100% synaptophysin positive. The histotype of synaptophysin-positive tumours (i.e. ≥20%) was not otherwise specified in 11 cases (61.1%) and mucinous adenocarcinoma in 4 cases (22.2%). Four cases were DNA mismatch repair deficient (22.2%) and 7 (38.9%) were characterized by a high number of tumour-infiltrating lymphocytes. At multivariate analysis, high synaptophysin expression was a negative independent prognostic factor for both PFS (HR = 2.00, 95% confidence interval [CI] 1.21-3.33, p = 0.006) and OS (HR = 2.27, 95% CI 1.35-3.85, p = 0.001). Among BRAFmt mCRCs, synaptophysin-positive tumours are characterized by worse PFS and OS. Further studies should investigate the molecular mechanisms involved in the acquisition of the neuroendocrine phenotype to identify novel-targeted treatment strategies.
Sections du résumé
BACKGROUND
Neuroendocrine differentiation has been extensively associated with worse prognosis and to mechanisms of therapy resistance in several epithelial cancers. A high prevalence of neuroendocrine differentiation was recently described in
METHODS
We assessed synaptophysin immunohistochemical expression in a multi-institutional series of 159 BRAFmt mCRCs with matched clinical and pathological information. Tumours were dichotomized as synaptophysin high and low. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier and log-rank tests.
RESULTS
Thirty-five tumours (22.0%) showed any level of positivity for synaptophysin, and 18 (11.3%) were characterized by positivity in at least 20% of tumour cells. Four cases resulted 100% synaptophysin positive. The histotype of synaptophysin-positive tumours (i.e. ≥20%) was not otherwise specified in 11 cases (61.1%) and mucinous adenocarcinoma in 4 cases (22.2%). Four cases were DNA mismatch repair deficient (22.2%) and 7 (38.9%) were characterized by a high number of tumour-infiltrating lymphocytes. At multivariate analysis, high synaptophysin expression was a negative independent prognostic factor for both PFS (HR = 2.00, 95% confidence interval [CI] 1.21-3.33, p = 0.006) and OS (HR = 2.27, 95% CI 1.35-3.85, p = 0.001).
CONCLUSIONS
Among BRAFmt mCRCs, synaptophysin-positive tumours are characterized by worse PFS and OS. Further studies should investigate the molecular mechanisms involved in the acquisition of the neuroendocrine phenotype to identify novel-targeted treatment strategies.
Identifiants
pubmed: 33607478
pii: S0959-8049(21)00028-9
doi: 10.1016/j.ejca.2021.01.016
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
SYP protein, human
0
Synaptophysin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-154Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare no conflict of interest regarding the publication of this article. Matteo Fassan received research grant from Astellas Pharma and QED Therapeutics and is a consultant/advisory board member for Astellas Pharma, Diaceutics, Tesaro and GSK. Fotios Loupakis received lecture fees from Amgen and F. Hoffmann-La Roche and advisory fees from Bayer and Genentech. Sara Lonardi received advisory board fees from Amgen, Bayer, Eli Lilly, and Merck Serono, received research grant from Amgen and Merck Serono and is part of the speakers' bureau of Lilly and BMS. Angelo Paolo Dei Tos declares personal fees for advisory boards/speaker's bureau from PharaMar, Lilly, Roche, Bayer and Pfizer. Filippo Pietrantonio declared honoraria/speaker's bureau from Roche, Amgen, Merck-Serono, Lilly, Sanofi, Bayer and Servier and research grant from BMS. Chiara Cremolini is a consultant/advisory board member for Roche, Amgen, Bayer, Merck Serono and Servier. Massimo Di Maio received honoraria, had roles as a consultant or advisor for AstraZeneca, Bristol Myears Squibb, MSD, Takeda and Janssen and received a research grant from Tesaro. Vittorina Zagonel received honoraria and had roles as a consultant or advisor for Bristol-Myears Squibb, Bayer, Roche, Pfizer, Janssen, Novartis, Astellas and Servier and had roles as a consultant or advisor for Celgene and Merck. Lorenza Rimassa reports personal fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Eli Lilly, Exelixis, Hengrui, Incyte, Ipsen, Merck Sharp & Dohme, Nerviano Medical Sciences, Roches Sanofi, AbbViem Gilead and reearch grants from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Eli Lilly, Exelixis, FibroGen, Incyte, Ipsen, Merck Sharp & Dohme and Roche. Giuseppe Aprile reports receiving personal fees and has been a consultant for Merck Serono, Amgen, Roche and Servier.