Assessment of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in Breast Cancer Tissue: Historical Aspects and Future Prospects

Schmitt, Manfred; Mengele, Karin; Gkazepis, Apostolos; Napieralski, Rudolf; Magdolen, Viktor; Reuning, Ute; Harbeck, Nadia

doi:10.1159/000151737

Cited by 23 publications

(27 citation statements)

References 63 publications

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“…Moreover, an elevated expression of MMP-3 and uPA together appears to increase, altogether with the tumor grade and size; therefore our results are more alike to those in the literature, showing direct correlation between expression of uPA with high grade of the tumor, size, and lymphovascular invasion [31–33]. …”

Section: Discussionsupporting

confidence: 85%

“…Even though our results suggest an antimetastatic role for uPA, there are authors proposing exactly the opposite, that uPA might be a prometastatic molecule, since it is overexpressed in high grade tumors already with metastasis in lymphatic nodes [31–33]; the difference is that they did not make a comparison with tumors lacking metastatic ganglia, as we actually did.…”

Section: Discussioncontrasting

confidence: 83%

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Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City

Barajas-Castañeda

Cortés-Gutierrez

Rodríguez

et al. 2016

Journal of Immunology Research

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Extracellular matrix metalloproteases and the fibrinolytic system are important protease systems interacting with each other in charge of remodeling and recycling of tissues. Their role in tumor invasion and metastasis is often discussed. In this study several metalloproteases such as MMP-1, MMP-3, MMP-9, and TIMP-1 together with molecules from the fibrinolytic system like uPA, its receptor uPAR, and its inhibitor, PAI-1, were studied by immune-histochemistry to establish a comparison with and without metastasis. From the (118) primary tumors of Mexican patients with ductal breast cancer studied, 56% were grade II and 69% were size T2; the group with metastatic ganglia included 64 samples (54.3%). In patients with metastasis the estimated expression of MMP-3 and uPA (resp., 28% and 45%) was higher than that from no metastatic tumors; it means there is higher expression of both markers in metastatic tumors (p < 0.05). At the same time, metastatic tumors showed statistically significant lower signal of PAI-1 (24%) than tumors without metastasis (p < 0.05). We concluded that overexpression of MMP-3 and uPA, altogether with diminished expression of PAI-1 from metastatic tumors, might be a crucial step towards metastasis in ductal breast cancer. Nevertheless, additional studies in different populations are necessary to establish a pattern.

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Section: Discussionsupporting

confidence: 85%

Section: Discussioncontrasting

confidence: 83%

Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City

Barajas-Castañeda

Cortés-Gutierrez

Rodríguez

et al. 2016

Journal of Immunology Research

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“…However, tests based on immunohistochemistry are being explored. Using paraffin embedded tumor tissue would improve uptake of his test if the methods were validated [18]. Yet, if the infrastructure of collecting fresh frozen tissue can be implemented, the uPA/ PAI-1 test is feasible in clinical routine as demonstrated by our group.…”

Section: Discussionmentioning

confidence: 99%

Impact of guideline-based use of uPA/PAI-1 on patient outcome in intermediate-risk early breast cancer

Kolben

Augustin

Armbrust

et al. 2015

Breast Cancer Res Treat

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The purpose of this study was to evaluate the influence of guideline-based prospective use of uPA/PAI-1 on clinical outcome in an intermediate-risk cohort of breast cancer patients. We analyzed 381 consecutive primary breast cancer patients (2003-2011) at the breast center Ostbayern meeting the following criteria: M0/N0/estrogen receptor (ER)+/G2. Clinical-pathological data, uPA/PAI-1, and follow-up data were collected. Decisions for adjuvant chemotherapy were made upon consideration of prospectively measured uPA/PAI-1. Observed disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier estimates. Using guideline-based analysis of uPA/PAI-1, treatment with adjuvant chemotherapy was avoided in 86.5 % of patients with low uPA/PAI-1, i.e., 38.8 % of the total patient collective. Median follow-up was 52.5 months. Five-year relapse-free survival in intermediate-risk patients (N0, G2) without chemotherapy was 99 %. Five-year overall survival including all causes of death was 95 %. By using uPA/PAI-1, adjuvant chemotherapy can be avoided in a major part of patients with intermediate-risk breast cancer. Nevertheless, DFS and OS of these patients at 5 years remain excellent. The potential, but hardly measurable, benefit of adjuvant chemotherapy has to be set in contrast with its associated side effects and increased morbidity. Patients with high uPA/PAI-1 show benefit from chemotherapy. In this subgroup, a very good OS was observed as well. These findings strongly support the use of uPA/PAI-1 together with clinic-pathological parameters as an evidence-based, clinically relevant and inexpensive decision tool in the routine of a breast center.

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“…This included predictive markers for therapies targeting HER2 [50], diagnostic marker E-Cadherin [51], and prognostic markers including HER2, estrogen and progesterone receptors [42], and uPA and PAI-1 [52, 53]. To comprehensively assess protein heterogeneity further proteins connected to these candidates via signaling pathways were included, belonging either to the same protein family as the candidate proteins (EGFR, HER3, HER4, pPDGFR and VEGFR) or involved in downstream signaling of the candidate molecules (Akt, ERK, FAK, GSK3β, ILK, Integrin αV PTEN and STAT3).…”

Section: Resultsmentioning

confidence: 99%

“…In a research collaboration the intratumoral heterogeneity of defined proteins relevant to breast cancer was assessed using RPPA within primary breast cancers and between axillary lymph nither predictive markers for treatment stratification targeting HER2 [50], diagnostic marker E-Cadherin [51], or prognostic markers including HER2, estrogen and progesterone receptors [42], and uPA and PAI-1 [52, 53]. …”

Section: Introductionmentioning

confidence: 99%

Histopathological markers of treatment response and recurrence risk in ovarian cancers and borderline tumors

Avril

2017

Pathologe

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Assessment of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in Breast Cancer Tissue: Historical Aspects and Future Prospects

Cited by 23 publications

References 63 publications

Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City

Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City

Impact of guideline-based use of uPA/PAI-1 on patient outcome in intermediate-risk early breast cancer

Histopathological markers of treatment response and recurrence risk in ovarian cancers and borderline tumors

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