Impact of uPA/PAI-1 and disseminated cytokeratin-positive cells in breast cancer.
Aged
Aged, 80 and over
Biomarkers, Tumor
/ metabolism
Bone Marrow
/ pathology
Breast Neoplasms
/ metabolism
Disease Progression
Female
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Keratins
/ metabolism
Middle Aged
Neoplasm Staging
Neoplastic Cells, Circulating
/ metabolism
Plasminogen Activator Inhibitor 1
/ metabolism
Prognosis
Retrospective Studies
Urokinase-Type Plasminogen Activator
/ metabolism
Breast cancer
Circulating tumor cells
Prognosis
Proteases
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
15 Jul 2019
15 Jul 2019
Historique:
received:
31
10
2018
accepted:
20
06
2019
entrez:
17
7
2019
pubmed:
17
7
2019
medline:
18
12
2019
Statut:
epublish
Résumé
The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects. We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18. DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without chemotherapy, the prognostic impact of uPA and PAI-1 was enhanced in cases with additional dCK-positivity (triple +). In cases without chemotherapy, triple-positive status was independently prognostic (HR: 9.3 CI: 1.1-75) next to T stage. uPA and PAI-1 seem to influence the metastatic potential of dCK+ cells, which underlines its important role in tumor progression.
Sections du résumé
BACKGROUND
BACKGROUND
The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects.
METHODS
METHODS
We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18.
RESULTS
RESULTS
DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without chemotherapy, the prognostic impact of uPA and PAI-1 was enhanced in cases with additional dCK-positivity (triple +). In cases without chemotherapy, triple-positive status was independently prognostic (HR: 9.3 CI: 1.1-75) next to T stage.
CONCLUSIONS
CONCLUSIONS
uPA and PAI-1 seem to influence the metastatic potential of dCK+ cells, which underlines its important role in tumor progression.
Identifiants
pubmed: 31307406
doi: 10.1186/s12885-019-5857-0
pii: 10.1186/s12885-019-5857-0
pmc: PMC6632216
doi:
Substances chimiques
Biomarkers, Tumor
0
Plasminogen Activator Inhibitor 1
0
SERPINE1 protein, human
0
Keratins
68238-35-7
Urokinase-Type Plasminogen Activator
EC 3.4.21.73
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
692Références
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