nach oben

International Journal of Clinical Oncology

Erschienen in:

01.12.2014 | Original Article

A retrospective study of urokinase-type plasminogen activator receptor (uPAR) as a prognostic factor in cancer of the uterine cervix

verfasst von: Toru Sasaki, Hirotaka Nishi, Chie Nagata, Takeshi Nagai, Toshitaka Nagao, Fumitoshi Terauchi, Keiichi Isaka

Erschienen in: International Journal of Clinical Oncology | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

Hypoxia occurs during the development of uterine cervical cancer and is considered to correlate with its invasion. Hypoxia promotes both the invasiveness and the metastasis of cancer cells through urokinase-type plasminogen activator receptor (uPAR) expression. The aim of this study was to evaluate the correlation between uPAR mRNA level and clinical prognostic factors of uterine cervical cancer.

Methods

We performed a retrospective review of 59 patients with cervical cancer and 9 subjects with normal cervical tissues. Total RNA was isolated from tissues of the uterine cervix surgically removed from patients. The mRNA of uPAR could be measured by real time PCR (RT-PCR). Histopathological factors such as histopathological type, cervical stromal, parametrial, lymphovascular, and uterine corpus invasions, metastasis to the pelvic lymph nodes, and pTNM stage were confirmed by two pathologists. The examined prognostic factors alongside the histopathological ones were FIGO clinical stage, hemoglobin level, serum level of SCC, and the effect on clinical outcomes. These factors were statistically evaluated by Fisher’s exact test, log-rank test, and ROC analysis. Immunohistochemical staining with anti-uPAR monoclonal antibody was also performed.

Results

In uterine cervical cancer, overexpression of uPAR mRNA was significantly related to shorter disease-free survival (p = 0.0396). However, the other clinical prognostic and histopathological factors were not related to uPAR mRNA expression level. Immunohistochemical staining showed that positive staining for uPAR was histologically localized on the membrane of carcinoma cells. However, the staining was not very intense.

Conclusions

Overexpression of uPAR mRNA may be a prognostic factor in cancer of the uterine cervix.

CANCERMondial, GLOBOCAN 2008. (2013) Section of Cancer Information, International Agency for Research on Cancer. Available at: http://globocan.iarc.fr/

Nordsmark M, Overgaard M, Overgaard J (1996) Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 41:31–39PubMedCrossRef

Höckel M, Schlenger K, Aral B et al (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515PubMed

Dass K, Ahmad A, Azmi AS et al (2008) Evolving role of uPA/uPAR system in human cancers. Cancer Treat Rev 34:122–136PubMedCrossRef

Kwaan HC, McMahon B (2009) The role of plasminogen–plasmin system in cancer. Cancer Treat Res 148:43–66PubMedCrossRef

Büchler P, Reber HA, Tomlinson JS et al (2009) Transcriptional regulation of urokinase-type plasminogen activator receptor by hypoxia-inducible factor 1 is crucial for invasion of pancreatic and liver cancer. Neoplasia 11:196–206PubMedCentralPubMed

Kumano M, Miyake H, Muramaki M et al (2009) Expression of urokinase-type plasminogen activator system in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol Oncol 27:180–186PubMedCrossRef

Kotzsch M, Bernt K, Friedrich K et al (2010) Prognostic relevance of tumour cell-associated uPAR expression in invasive ductal breast carcinoma. Histopathology 57:461–471PubMedCrossRef

Smith R, Xue A, Gill A et al (2007) High expression of plasminogen activator inhibitor-2 (PAI-2) is a predictor of improved survival in patients with pancreatic adenocarcinoma. World J Surg 31:493–502PubMedCrossRef

10.

Zhang L, Zhao ZS, Ru GQ et al (2006) Correlative studies on uPA mRNA and uPAR mRNA expression with vascular endothelial growth factor, microvessel density, progression and survival time of patients with gastric cancer. World J Gastroenterol 12:3970–3976PubMedCentralPubMed

11.

Nishi H, Kuroda M, Isaka K (2013) Estrogen and estrogen receptor induce matrix metalloproteinase-26 expression in endometrial carcinoma cells. Oncol Rep 30:751–756PubMed

12.

Hasegawa E, Ito H, Hasegawa F et al (2012) Expression of leukemia inhibitory factor in the endometrium in abnormal uterine cavities during the implantation window. Fertil Steril 97:953–958PubMedCrossRef

13.

SAS Institute (1985) SAS user’s guide: statistics, Version5. SAS Institute, Cary, pp 529–557

14.

Ying J, Guo L, Qiu T et al (2013) Diagnostic value of a novel fully automated immunochemistry assay for detection of ALK rearrangement in primary lung adenocarcinoma. Ann Oncol 24(10):2589–2593PubMedCrossRef

15.

Foca C, Moses EK, Quinn MA et al (2000) Differential mRNA expression of urokinase-type plasminogen activator, plasminogen activator receptor and plasminogen activator inhibitor type-2 in normal human endometria and endometrial carcinomas. Gynecol Oncol 79:244–250PubMedCrossRef

16.

Halamkova J, Kiss I, Pavlovsky Z et al (2011) Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients. Neoplasma 58:377–385PubMedCrossRef

17.

Cantero D, Friess H, Deflorin J et al (1997) Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. Br J Cancer 75:388–395PubMedCentralPubMedCrossRef

18.

Almasi CE, Høyer-Hansen G, Christensen IJ et al (2005) Prognostic impact of liberated domain I of the urokinase plasminogen activator receptor in squamous cell lung cancer tissue. Lung Cancer 48:349–355PubMedCrossRef

19.

Friess H, Cantero D, Graber H et al (1997) Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis. Gastroenterology 113:904–913PubMedCrossRef

20.

Lund IK, Illemann M, Thurison T et al (2011) uPAR as anti-cancer target: evaluation of biomarker potential, histological localization, and antibody-based therapy. Curr Drug Targets 12:1744–1760PubMedCrossRef

21.

Hildenbrand R, Niedergethmann M, Marx A et al (2009) Amplification of the urokinase-type plasminogen activator receptor (uPAR) gene in ductal pancreatic carcinomas identifies a clinically high-risk group. Am J Pathol 174:2246–2253PubMedCentralPubMedCrossRef

22.

Bianchi E, Cohen RL, Thor AT et al (1994) The urokinase receptor is expressed in invasive breast cancer but not in normal breast tissue. Cancer Res 15:861–866

23.

Pyke C, Kristensen P, Ralfkiaer E et al (1991) Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol 138:1059–1067PubMedCentralPubMed

24.

Arvelo F, Cotte C (2009) Hypoxia in cancer malignity. Review. Inv Clin 50:529–546

25.

Lu X, Kang Y (2010) Hypoxia and hypoxia-inducible factors: master regulators of metastasis. Clin Cancer Res 16:5928–5935PubMedCentralPubMedCrossRef

Titel: A retrospective study of urokinase-type plasminogen activator receptor (uPAR) as a prognostic factor in cancer of the uterine cervix
verfasst von: Toru Sasaki
Hirotaka Nishi
Chie Nagata
Takeshi Nagai
Toshitaka Nagao
Fumitoshi Terauchi
Keiichi Isaka
Publikationsdatum: 01.12.2014
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 6/2014
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-014-0664-8

Neu im Fachgebiet Onkologie

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Springer Medizin

A retrospective study of urokinase-type plasminogen activator receptor (uPAR) as a prognostic factor in cancer of the uterine cervix