Clinical Relevance of Urokinase-Type Plasminogen Activator, Its Receptor, and Its Inhibitor Type 1 in Endometrial Cancer

Tecimer, C.; Doering, David L.; Goldsmith, L. Jane; Meyer, John S.; Abdulhay, Gazi; Wittliff, James L.

doi:10.1006/gyno.2000.6015

Cited by 42 publications

(27 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18 In this respect our data are in concordance with results of a smaller study of endometrial cancer, in which uPAR did not associate with disease-free survival but with uPA. 19 Somewhat in contrast, we found that high tumor tissue level of uPAR was associated with early clinical stage and well-differentiated tumor histology, which are known to associate with better prognosis. 27 The biologic relevance of these correlations is not obvious.…”

Section: Discussioncontrasting

confidence: 55%

“…[13][14][15][16][17] High tumor tissue concentrations of uPA and PAI-1 have also been associated with poor prognosis in endometrial cancer. 18,19 In contrast, high levels of PAI-2 have been associated with better prognosis in subgroups of patients with breast cancer 15,20,21 but were associated with aggressive disease in colorectal 22 and ovarian cancer. 23,24 In the present study we evaluated the association between tumor tissue levels of PAI-2 and uPAR and endometrial cancer patient survival.…”

mentioning

confidence: 99%

See 1 more Smart Citation

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

Nordengren

Lidebring

Bendahl

et al. 2001

Intl Journal of Cancer

View full text Add to dashboard Cite

Previous studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI-2) and patient survival. High tumor tissue concentrations of PAI-2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI-1 have more consistently been associated with poor histologic differentiation and poor prognosis. Our study quantified PAI-2 and uPAR using specific enzyme-linked immunosorbent assays in homogenates of 274 samples of endometrial cancer tissue. The prognostic power of each factor was analyzed in the subgroup of patients with early stage disease, i.e., International Federation of Gynecology and Oncology (FIGO) surgical stage I-II (n ‫؍‬ 188). This group had a median follow-up time of 6.8 years (range 0.7-9.9), and 23 progressions were observed. The 80 th percentile for PAI-2 and uPAR was used to dichotomize the material, and the results were analyzed for associations with clinical data including progression-free survival. The results were also compared with DNA ploidy status, S-phase fraction, uPA and PAI-1, which we reported in a previous study (Fredstorp Lidebring et al., Eur J Cancer 2001; in press). A high PAI-2 level was associated with shorter progression-free survival in univariate analysis and was an independent prognostic factor in bivariate analyses, which included PAI-1, uPA and DNA ploidy status. In contrast, a high level of uPAR had no association with prognosis in early stage endometrial cancer. The combination of high PAI-2 and PAI-1 levels in tumors revealed a small group of stage I-II patients with an accumulative progression rate of 50%.

show abstract

Section: Discussioncontrasting

confidence: 55%

mentioning

confidence: 99%

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

Nordengren

Lidebring

Bendahl

et al. 2001

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…A 33-fold increase in UPAR mRNA levels was observed, from normal endometria to advanced clinical stage carcinomas and showed a near linear increase with each progression in clinical stage (10). Tecimer et al (29) assessed UPA, UPAR, and PAI-1 levels in extracts of endometrial cancer tissue by using ELISA and correlated their expression levels with tumor histology, stage and grade of disease, and recurrence rate. Although PAI-1 was a predictor of survival, in these studies UPAR did not show any significant correlation (29).…”

Section: Discussionmentioning

confidence: 99%

“…Tecimer et al (29) assessed UPA, UPAR, and PAI-1 levels in extracts of endometrial cancer tissue by using ELISA and correlated their expression levels with tumor histology, stage and grade of disease, and recurrence rate. Although PAI-1 was a predictor of survival, in these studies UPAR did not show any significant correlation (29). More recently, Nordengren et al (30) quantified UPAR protein by ELISA in homogenates of 274 samples of endometrial cancer tissue and found no correlation with patient survival; however, only patients with FIGO surgical stage I-II were used in their study.…”

Section: Discussionmentioning

confidence: 99%

Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer

Memarzadeh

Kozak

Chang

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. However, reliable diagnostic or prognostic tumor markers have not been identified for endometrial cancer. In this study, we examined whether urokinase plasminogen activator receptor (UPAR), a glycosyl-phosphatidylinositol-linked membrane protein, is a candidate diagnostic or prognostic marker for patients with cancer of the endometrium. Sixty-five surgically excised, formalin-fixed endometrial tissue specimens were accessioned through the Department of Pathology Registry at the University of California, Los Angeles, and analyzed for UPAR expression by using immunohistochemical techniques. A retrospective review was also performed to determine stage and histopathologic grade of disease, recurrence, and mortality. No expression of UPAR protein was present in seven patients with benign neoplasia of the endometrium. UPAR protein expression highly correlated with stage of disease (ungrouped Spearman correlation = 0.625, P < 0.0001): 40% of patients with stage I, 66% of patients with stage II, 100% of patients with stage III, and 85% with stage IV demonstrated the highest level of UPAR expression. Moreover, high UPAR expression positively correlated with grade of disease (ungrouped Spearman correlation = 0.71, P < 0.0001): 29% of grade 1 specimens, 57% of grade 2, and over 90% of specimens with grade 3, the majority representing uterine papillary serous carcinoma and mixed malignant mesodermal tumor. Finally, UPAR protein expression also positively correlated with rate of recurrence and mortality in patients with adenocarcinoma of the endometrium (ungrouped P = 0.034). Our data suggest that UPAR is a useful prognostic marker for biologically aggressive forms of endometrial cancer

show abstract

“…Both studies showed no significant association between uPAR and disease free survival or OS. 85,86 This lack of association between high uPAR and prognosis may be explained by the fact that tumor differentiation also did not associate with progression free survival, or may reflect the use of ELISA to analyze uPAR expression. It has been argued that the ambiguity of the results above may be a consequence of heterogeneous tumor tissue homogenate, with contamination of ''well-differentiated'' tissue in poorly differentiated tissue and vice versa, concealing any real statistically significant differences.…”

Section: E Endometrial Cancermentioning

confidence: 82%

Clinical significance of urokinase‐type plasminogen activator receptor (uPAR) expression in cancer

Bock

Wang

2003

Medicinal Research Reviews

135

103

View full text Add to dashboard Cite

The involvement of the urokinase-type plasminogen activator (uPA) system in particular has been extensively studied in the pathogenesis of cancer. The molecular role of the uPA receptor (uPAR) is well characterized with its participation in cell migration and extracellular matrix (ECM) degradation. Over-expression of uPAR in cancer has been demonstrated in many studies and is considered an attractive target for anticancer agents. We and others have down-regulated uPAR expression in an attempt to inhibit cancer metastasis based on its molecular role. Uniquely, uPAR which is a glycosyl phosphatidylinositol anchored protein is not only bound to the cell surface but also has a soluble form, suPAR. There is now accumulated clinical and experimental evidence supporting the significant role of uPAR and its soluble counterpart in a number of solid cancers. The expression of uPAR can be associated with tumor cells or stromal cells or both. Differences observed in the expression of uPAR using immunohistochemistry (IHC) are likely explained by the use of different antibodies and techniques rather than true cellular differences and are reviewed here. This review summarizes the clinical relevance of uPAR and its soluble form in the prognosis and diagnosis of different cancers.

show abstract

Clinical Relevance of Urokinase-Type Plasminogen Activator, Its Receptor, and Its Inhibitor Type 1 in Endometrial Cancer

Cited by 42 publications

References 36 publications

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer

Clinical significance of urokinase‐type plasminogen activator receptor (uPAR) expression in cancer

Contact Info

Product

Resources

About