The prognostic relevance of FOXA1 and Nestin expression in breast cancer metastases: a retrospective study of 164 cases during a 10-year period (2004-2014).
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Breast Neoplasms
/ epidemiology
Female
Gene Expression
Hepatocyte Nuclear Factor 3-alpha
/ genetics
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Nestin
/ genetics
Prognosis
Proportional Hazards Models
Retrospective Studies
Sweden
/ epidemiology
Breast cancer metastases
FOXA1
GATA3
Immunohistochemistry
Nestin
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
28 Feb 2019
28 Feb 2019
Historique:
received:
28
09
2018
accepted:
17
02
2019
entrez:
2
3
2019
pubmed:
2
3
2019
medline:
14
6
2019
Statut:
epublish
Résumé
Current prognostic markers cannot adequately predict the clinical outcome of breast cancer patients. Therefore, additional biomarkers need to be included in routine immune panels. FOXA1 was a significant predictor of favorable outcome in primary breast cancer, while Nestin expression is preferentially found in triple-negative tumors with increased rate of nodal metastases, and reduced survival. No studies have investigated the prognostic value of FOXA1 and Nestin expression in breast cancer metastases. Breast cancer metastases (n = 164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression. Cox regression analysis assessed the prognostic value of FOXA1 and Nestin expression. In breast cancer metastases, FOXA1 expression was associated with Nestin-negativity, GATA3-positivity, ER-positivity, HER2-positivity and non-triple-negative status (P < 0.05). In contrast, Nestin expression was associated with FOXA1-negative, GATA3-negative, ER-negative, and triple-negative metastases (P < 0.05). Univariate Cox regression analysis showed FOXA1 expression was predictive of overall survival (OS, P = 0.00048) and metastasis-free survival (DMFS, P = 0.0011), as well as, distant metastasis-free survival in ER-positive patients (P = 0.036) and overall survival in ER-negative patients (P = 0.024). Multivariate analysis confirmed the significance of FOXA1 for both survival endpoints in metastatic breast cancer patients (OS, P = 0.0033; DMFS, P = 0.015). In our study, FOXA1 was expressed mostly in ER-positive breast cancer metastases. Expression of Nestin was related to triple-negative metastases, where brain was the most frequent metastatic site. These findings highlight the clinical utility of FOXA1 and Nestin expression and warrant their inclusion in routine immunohistochemical panels for breast carcinoma.
Sections du résumé
BACKGROUND
BACKGROUND
Current prognostic markers cannot adequately predict the clinical outcome of breast cancer patients. Therefore, additional biomarkers need to be included in routine immune panels. FOXA1 was a significant predictor of favorable outcome in primary breast cancer, while Nestin expression is preferentially found in triple-negative tumors with increased rate of nodal metastases, and reduced survival. No studies have investigated the prognostic value of FOXA1 and Nestin expression in breast cancer metastases.
METHODS
METHODS
Breast cancer metastases (n = 164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression. Cox regression analysis assessed the prognostic value of FOXA1 and Nestin expression.
RESULTS
RESULTS
In breast cancer metastases, FOXA1 expression was associated with Nestin-negativity, GATA3-positivity, ER-positivity, HER2-positivity and non-triple-negative status (P < 0.05). In contrast, Nestin expression was associated with FOXA1-negative, GATA3-negative, ER-negative, and triple-negative metastases (P < 0.05). Univariate Cox regression analysis showed FOXA1 expression was predictive of overall survival (OS, P = 0.00048) and metastasis-free survival (DMFS, P = 0.0011), as well as, distant metastasis-free survival in ER-positive patients (P = 0.036) and overall survival in ER-negative patients (P = 0.024). Multivariate analysis confirmed the significance of FOXA1 for both survival endpoints in metastatic breast cancer patients (OS, P = 0.0033; DMFS, P = 0.015).
CONCLUSIONS
CONCLUSIONS
In our study, FOXA1 was expressed mostly in ER-positive breast cancer metastases. Expression of Nestin was related to triple-negative metastases, where brain was the most frequent metastatic site. These findings highlight the clinical utility of FOXA1 and Nestin expression and warrant their inclusion in routine immunohistochemical panels for breast carcinoma.
Identifiants
pubmed: 30819139
doi: 10.1186/s12885-019-5373-2
pii: 10.1186/s12885-019-5373-2
pmc: PMC6394077
doi:
Substances chimiques
Biomarkers, Tumor
0
FOXA1 protein, human
0
Hepatocyte Nuclear Factor 3-alpha
0
Nestin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
187Références
J Clin Pathol. 2008 Mar;61(3):327-32
pubmed: 18037662
Eur J Cancer. 2008 Jul;44(11):1541-51
pubmed: 18538561
J Clin Pathol. 2008 Sep;61(9):1045-50
pubmed: 18641405
Expert Rev Mol Med. 2009 Mar 05;11:e8
pubmed: 19261198
Breast Cancer Res. 2009;11(3):R40
pubmed: 19549328
Mod Pathol. 2010 Feb;23(2):270-5
pubmed: 19946260
Genome Res. 2011 Jan;21(1):47-55
pubmed: 21147910
Breast Cancer Res Treat. 2012 Feb;131(3):881-90
pubmed: 21503684
EMBO J. 2011 Sep 20;30(19):3885-94
pubmed: 21934649
Eur J Histochem. 2011 Nov 14;55(4):e39
pubmed: 22297445
Horm Cancer. 2012 Aug;3(4):147-59
pubmed: 22476979
Nat Genet. 2012 May 20;44(6):685-9
pubmed: 22610119
Nature. 2012 Jul 12;487(7406):239-43
pubmed: 22722839
Front Oncol. 2013 Feb 14;3:20
pubmed: 23420418
Breast Cancer. 2015 May;22(3):308-16
pubmed: 23771556
Breast Cancer. 2015 Sep;22(5):520-8
pubmed: 24415069
Asian Pac J Cancer Prev. 2014;15(1):11-6
pubmed: 24528009
Br J Cancer. 2015 Jan 20;112(2):345-51
pubmed: 25422910
Sci Adv. 2016 Mar 18;2(3):e1501473
pubmed: 27034986
Biochem Biophys Res Commun. 2017 Apr 1;485(2):522-528
pubmed: 28189679
J Biol Chem. 2017 May 19;292(20):8136-8148
pubmed: 28270510
Sci Rep. 2017 Apr 24;7(1):1089
pubmed: 28439082
Ecancermedicalscience. 2017 Apr 07;11:732
pubmed: 28491135
Breast Care (Basel). 2017 May;12(2):102-107
pubmed: 28559767
Int J Oncol. 2017 Aug;51(2):668-676
pubmed: 28656248
Breast J. 2018 Mar;24(2):184-188
pubmed: 28703335
Biol Pharm Bull. 2017;40(9):1483-1489
pubmed: 28867731
Eur Rev Med Pharmacol Sci. 2017 Sep;21(18):4137-4140
pubmed: 29028085
Breast Cancer Res Treat. 2018 Feb;168(1):107-115
pubmed: 29159761
Int J Oncol. 2018 Feb;52(2):527-535
pubmed: 29345290
Br J Cancer. 2018 Jul;119(1):76-79
pubmed: 29880907
Mol Oncol. 2018 Nov;12(11):1884-1894
pubmed: 29972720