Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer

Abstract

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

Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy

“…DKK1, for example, has been recently reported by our group to play an important role in the development of osteolytic lesions in multiple myeloma (Tian et al, 2003), but its possible role in USPC pathogenesis and/or progression has not been elucidated. For other genes such as UPAR, a glycosylphosphatidylinositol-anchored glycoprotein whose role in promoting tumour cell invasion and metastases has been well established in a number of experimental studies, a correlation with high expression in the USPC phenotype has been recently reported (Memarzadeh et al, 2002). A large number of downregulated (at least five-fold) genes in USPC vs NEC, such as transforming growth factor beta receptor III, platelet-derived growth factor receptor alpha, SEMACAP3, ras homolog gene family member I (ARHI), and DOC1 (Table 3), have been identified in our analysis.…”

Real‐time quantitative PCR determination of urokinase‐type plasminogen activator receptor (uPAR) expression of isolated micrometastatic cells from bone marrow of breast cancer patients

“…Memarzadeh et al 16 analyzed uPAR expression by immunohistochemistry in 65 primary endometrial tumors and showed that high uPAR expression in primary tumors was positively correlated with the grade of the disease and also positively correlated with recurrence and mortality rates in patients with adenocarcinoma of the endometrium. Heiss et al 20 were the first to demonstrate uPAR expression analyzed by IHC in the bone marrow of patients with gastric carcinoma as an independent prognostic factor for disease-free and overall survival.…”

Increased expression of metastasis-related genes in hypoxic cells sorted from cervical and lymph nodal xenograft tumors

“…38,39 uPAR staining was observed to be localized in the cytoplasm, but specific regions showed membrane staining consistent with literature reports. 40 Hdm2 stained positive in both the nucleus and cytoplasm. The staining of OPN appeared in the cytoplasm with slight membrane staining of tumor cells in both the primary cervix and the lymph node tumors.…”