Prognostic Value Analysis of Urokinase-type Plasminogen Activator Receptor in Oral Squamous Cell Carcinoma: an Immunohistochemical Study

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2008 Aug 5

PMID 18673553

Citations 10

Authors

Roberta Bacchiocchi

Corrado Rubini

Elisa Pierpaoli

Giulia Borghetti

Pasquale Procacci

Pier Francesco Nocini

Andrea Santarelli

Romina Rocchetti

Domenico Ciavarella

Lorenzo Lo Muzio

Francesca Fazioli

Affiliations

Soon will be listed here.

Abstract

Background: Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia.

Methods: In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate.

Results: In our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives.

Conclusion: The results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients.

Citing Articles

Expression patterns of uPAR, TF and EGFR and their potential as targets for molecular imaging in oropharyngeal squamous cell carcinoma.

Christensen A, Gronhoj C, Jensen J, Lelkaitis G, Kiss K, Juhl K Oncol Rep. 2022; 48(2).

PMID: 35775375 PMC: 9263836. DOI: 10.3892/or.2022.8359.

Epiregulin promotes trophoblast epithelial-mesenchymal transition through poFUT1 and O-fucosylation by poFUT1 on uPA.

Cui X, Wang H, Li Y, Chen T, Liu S, Yan Q Cell Prolif. 2020; 53(2):e12745.

PMID: 31889361 PMC: 7046484. DOI: 10.1111/cpr.12745.

Improved surgical resection of metastatic pancreatic cancer using uPAR targeted fluorescent guidance: comparison with traditional white light surgery.

Juhl K, Christensen A, Rubek N, Karnov K, von Buchwald C, Kjaer A Oncotarget. 2019; 10(59):6308-6316.

PMID: 31695839 PMC: 6824874. DOI: 10.18632/oncotarget.27220.

PLOD3 promotes lung metastasis via regulation of STAT3.

Baek J, Yun H, Kwon G, Kim J, Lee C, Song J Cell Death Dis. 2018; 9(12):1138.

PMID: 30442941 PMC: 6237925. DOI: 10.1038/s41419-018-1186-5.

SUOX is negatively associated with multistep carcinogenesis and proliferation in oral squamous cell carcinoma.

Nakamura K, Akiba J, Ogasawara S, Naito Y, Nakayama M, Abe Y Med Mol Morphol. 2017; 51(2):102-110.

PMID: 29280012 DOI: 10.1007/s00795-017-0177-4.

References

Pedersen H, Brunner N, Francis D, Osterlind K, Ronne E, Hansen H . Prognostic impact of urokinase, urokinase receptor, and type 1 plasminogen activator inhibitor in squamous and large cell lung cancer tissue. Cancer Res. 1994; 54(17):4671-5. View

Schliephake H . Prognostic relevance of molecular markers of oral cancer--a review. Int J Oral Maxillofac Surg. 2003; 32(3):233-45. DOI: 10.1054/ijom.2002.0383. View

Peters H, van Putten W, Look M, Pappot H, Ronne E, Dano K . Prognostic significance of the receptor for urokinase plasminogen activator in breast cancer. Clin Cancer Res. 1995; 1(10):1079-87. View

Vivani C, Magi S, Mazzucchelli R, Bacchiocchi R, Santinelli A, Muzzonigro G . Immunohistochemical evaluation of urokinase plasminogen activator receptor in noninvasive and early invasive urothelial papillary neoplasia. Anal Quant Cytol Histol. 2004; 26(1):15-21. View

Rabbani S . Metalloproteases and urokinase in angiogenesis and tumor progression. In Vivo. 1998; 12(1):135-42. View

Casslen B, Gustavsson B, ASTEDT B . Cell membrane receptors for urokinase plasminogen activator are increased in malignant ovarian tumours. Eur J Cancer. 1991; 27(11):1445-8. DOI: 10.1016/0277-5379(91)90028-c. View

Wang J, Guo F, Wei H, Dong J, Wu J . Expression of urokinase-type plasminogen activator receptor is correlated with metastases of lingual squamous cell carcinoma. Br J Oral Maxillofac Surg. 2005; 44(6):515-9. DOI: 10.1016/j.bjoms.2005.10.009. View

Lindberg P, Larsson A, Nielsen B . Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma. Int J Cancer. 2006; 118(12):2948-56. DOI: 10.1002/ijc.21568. View

Ghosh S, Munshi H, Sen R, Linz-McGillem L, Goldman R, Lorch J . Loss of adhesion-regulated proteinase production is correlated with invasive activity in oral squamous cell carcinoma. Cancer. 2002; 95(12):2524-33. DOI: 10.1002/cncr.10997. View

10.

Ronne E, Behrendt N, Ellis V, Ploug M, Dano K, Hoyer-Hansen G . Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2-terminal domain of the urokinase receptor. FEBS Lett. 1991; 288(1-2):233-6. DOI: 10.1016/0014-5793(91)81042-7. View

11.

Blasi F . uPA, uPAR, PAI-1: key intersection of proteolytic, adhesive and chemotactic highways?. Immunol Today. 1997; 18(9):415-7. DOI: 10.1016/s0167-5699(97)01121-3. View

12.

Welkoborsky H, Gluckman J, Jacob R, BERNAUER H, Mann W . [Tumor biologic prognostic parameters in T1N0M0 squamous cell carcinoma of the oral cavity]. Laryngorhinootologie. 1999; 78(3):131-8. DOI: 10.1055/s-2007-996845. View

13.

Nozaki S, Endo Y, Kawashiri S, Nakagawa K, Yamamoto E, Yonemura Y . Immunohistochemical localization of a urokinase-type plasminogen activator system in squamous cell carcinoma of the oral cavity: association with mode of invasion and lymph node metastasis. Oral Oncol. 1998; 34(1):58-62. DOI: 10.1016/s1368-8375(97)00028-6. View

14.

Ghosh S, Johnson J, Sen R, Mukhopadhyay S, Liu Y, Zhang F . Functional relevance of urinary-type plasminogen activator receptor-alpha3beta1 integrin association in proteinase regulatory pathways. J Biol Chem. 2006; 281(19):13021-13029. DOI: 10.1074/jbc.M508526200. View

15.

Ganesh S, Sier C, Heerding M, Griffioen G, Lamers C, Verspaget H . Urokinase receptor and colorectal cancer survival. Lancet. 1994; 344(8919):401-2. DOI: 10.1016/s0140-6736(94)91427-3. View

16.

Ganesh S, Sier C, Heerding M, van Krieken J, Griffioen G, Welvaart K . Prognostic value of the plasminogen activation system in patients with gastric carcinoma. Cancer. 1996; 77(6):1035-43. DOI: 10.1002/(sici)1097-0142(19960315)77:6<1035::aid-cncr5>3.0.co;2-g. View

17.

Schmidt M, Schler G, Gruensfelder P, Muller J, Hoppe F . Urokinase receptor up-regulation in head and neck squamous cell carcinoma. Head Neck. 2000; 22(5):498-504. DOI: 10.1002/1097-0347(200008)22:5<498::aid-hed9>3.0.co;2-w. View

18.

Clayman G, Wang S, Nicolson G, El-Naggar A, Mazar A, Henkin J . Regulation of urokinase-type plasminogen activator expression in squamous-cell carcinoma of the oral cavity. Int J Cancer. 1993; 54(1):73-80. DOI: 10.1002/ijc.2910540113. View

19.

Ghosh S, Brown R, Jones J, Ellerbroek S, Stack M . Urinary-type plasminogen activator (uPA) expression and uPA receptor localization are regulated by alpha 3beta 1 integrin in oral keratinocytes. J Biol Chem. 2000; 275(31):23869-76. DOI: 10.1074/jbc.M000935200. View

20.

Shi Z, Stack M . Urinary-type plasminogen activator (uPA) and its receptor (uPAR) in squamous cell carcinoma of the oral cavity. Biochem J. 2007; 407(2):153-9. DOI: 10.1042/BJ20071037. View