PLC-gamma-1 phosphorylation status is prognostic of metastatic risk in patients with early-stage Luminal-A and -B breast cancer subtypes.
Aged
Biomarkers, Tumor
/ metabolism
Breast Neoplasms
/ metabolism
Female
Follow-Up Studies
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Ki-67 Antigen
/ metabolism
Menopause
/ physiology
Middle Aged
Multivariate Analysis
Neoplasm Metastasis
Neoplasm Recurrence, Local
Neoplasm Staging
Phospholipase C gamma
/ metabolism
Phosphorylation
Prognosis
Proportional Hazards Models
Receptor, ErbB-2
/ metabolism
Receptors, Estrogen
/ metabolism
Receptors, Progesterone
/ metabolism
Retrospective Studies
Breast cancer
Luminal subtypes
Menopausal status
Phospholipase Cγ1
Prognosis
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
30 Jul 2019
30 Jul 2019
Historique:
received:
29
12
2018
accepted:
17
07
2019
entrez:
1
8
2019
pubmed:
1
8
2019
medline:
1
1
2020
Statut:
epublish
Résumé
Phospholipase Cγ1 (PLCγ1) is highly expressed in human tumours. Our previous studies reported that both stable and inducible PLCγ1 down-regulation can inhibit formation of breast-cancer-derived experimental lung metastasis. Further, high expression of PLCγ1 and its constitutively activated forms (i.e., PLCγ1-pY1253, PLCγ1-pY783) is associated with worse clinical outcome in terms of incidence of distant metastases, but not of local relapse in T1-T2, N0 breast cancer patients. In the present retrospective study, we analysed the prognostic role of PLCγ1 in early breast cancer patients stratified according to the St. Gallen criteria and to their menopausal status. PLCγ1-pY1253 and PLCγ1-pY783 protein expression levels were determined by immunohistochemistry on tissue microarrays, and were correlated with patients' clinical data, using univariate and multivariate statistical analyses. In our series, the prognostic value of PLCγ1 overexpression was restricted to Luminal type tumours. From multivariate analyses, pY1253-PLCγ1 PLCγ1 overexpression is a strong predictive surrogate marker of development of metastases in early Luminal-A and -B breast cancer patients, being able to discriminate patients with high and low risk of metastases. Therefore, targeting the PLCγ1 pathway can be considered of potential benefit for prevention of metastatic disease.
Sections du résumé
BACKGROUND
BACKGROUND
Phospholipase Cγ1 (PLCγ1) is highly expressed in human tumours. Our previous studies reported that both stable and inducible PLCγ1 down-regulation can inhibit formation of breast-cancer-derived experimental lung metastasis. Further, high expression of PLCγ1 and its constitutively activated forms (i.e., PLCγ1-pY1253, PLCγ1-pY783) is associated with worse clinical outcome in terms of incidence of distant metastases, but not of local relapse in T1-T2, N0 breast cancer patients.
METHODS
METHODS
In the present retrospective study, we analysed the prognostic role of PLCγ1 in early breast cancer patients stratified according to the St. Gallen criteria and to their menopausal status. PLCγ1-pY1253 and PLCγ1-pY783 protein expression levels were determined by immunohistochemistry on tissue microarrays, and were correlated with patients' clinical data, using univariate and multivariate statistical analyses.
RESULTS
RESULTS
In our series, the prognostic value of PLCγ1 overexpression was restricted to Luminal type tumours. From multivariate analyses, pY1253-PLCγ1
CONCLUSIONS
CONCLUSIONS
PLCγ1 overexpression is a strong predictive surrogate marker of development of metastases in early Luminal-A and -B breast cancer patients, being able to discriminate patients with high and low risk of metastases. Therefore, targeting the PLCγ1 pathway can be considered of potential benefit for prevention of metastatic disease.
Identifiants
pubmed: 31362705
doi: 10.1186/s12885-019-5949-x
pii: 10.1186/s12885-019-5949-x
pmc: PMC6668079
doi:
Substances chimiques
Biomarkers, Tumor
0
Ki-67 Antigen
0
MKI67 protein, human
0
Receptors, Estrogen
0
Receptors, Progesterone
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Phospholipase C gamma
EC 3.1.4.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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