Zelluläres Fibronektin - ein Marker für muskelinvasive Harnblasenkarzinome

Zusammenfassung

Fragestellung: Bis heute existieren für das Transitionalzellkarzinom der Harnblase (TCC) keine verlässlichen Marker. Fibronektin, ein Glykoprotein der extrazellulären Matrix, unterstützt die lokale Tumorprogression und -invasion. Ziel der Studie war es, die Wertigkeit von zellulärem Fibronektin (cFN) im Plasma von Patienten mit unterschiedlichen TCC-Stadien zu evaluieren. Methoden: Blutproben von 41 Patienten mit TCC wurden vor Durchführung einer transurethralen Tumorresektion entnommen. 60 Patienten mit gutartigen urologischen Erkrankungen dienten als Kontrollgruppe. cFN wurde mittels eines selbstentwickelten, hochsensitiven „time resolved fluorescence immunoassay (TRFIA)” bestimmt. Ergebnisse: Patienten mit TCC zeigten signifikant höhere cFN-Plasmaspiegel als die Kontrollgruppe (p < 0,02). Zusätzlich wiesen Patienten mit muskelinvasiven Stadien (n = 14) signifikant höhere cFN-Werte als Patienten mit oberflächlichem TCC (n = 27, p < 0,05) auf. Schlussfolgerungen: Die erhobenen Daten unterstreichen die Wertigkeit, aber noch unklare Rolle von cFN beim TCC. Da muskelinvasive Stadien signifikant höhere cFN-Plasmaspiegel aufweisen, müssen aktuelle Langzeituntersuchungen den Stellenwert von cFN im Rahmen der Nachsorge und als Prognosefaktor klären.

Abstract

Background: Up to now reliable markers for transitional cell carcinoma of the bladder (TCC) are missing. Fibronectin, an extracellular matrix glycoprotein supports tumor progression and invasion. In the present study the role of cellular fibronectin (cFN) as a tumor marker in different stages of TCC has been evaluated. Methods: Blood samples of 41 patients with TCC were collected before they underwent transurethral tumor resection. 60 patients with non-malignant urological diseases served as controls. cFN was determined using a highly sensitive time resolved fluorescence immunoassay (TRFIA) developed in our laboratory. Results: In patients with TCC significant elevated cFN plasma levels were found compared to controls (p < 0.02). Additionally, patients with muscle invasive TCC (n = 14) demonstrated significantly higher cFN plasma levels compared to patients with superficial TCC (n = 27, p < 0.05). Conclusions: In the face of significantly higher cFN plasma levels in TCC our data underline the important role of cFN for tumor genesis and progression and its potential role as a marker for TCC. The elevated cFN levels found in locally advanced disease here are of high interest for future follow-up studies evaluating superficial tumor stages and the impact of cFN as a prognostic factor.

Schlüsselwörter

Tumormarker - extrazelluläre Matrix - Prognosefaktor - Tumorprogression

Key words

Tumormarker - extracellular matrix - prognostic factor - tumor progression

Literatur

• 1 Heney N M. Natural history of superficial bladder cancer. Prognostic features and long-term disease course.  Urol Clin North Am. 1992;  19 429-433
• 2 Gwynn E S, Clark P E. Bladder cancer.  Curr Opin Oncol. 2006;  18 277-283
• 3 Kataja V V, Pavlidis N. ESMO Guidelines Task Force. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of invasive bladder cancer.  Ann Oncol. 2005;  16 (Suppl 1) i43-44
• 4 Kirkali Z, Chan T, Manoharan M. et al . Bladder cancer: epidemiology, staging and grading, and diagnosis.  Urology. 2005;  66 (6 Suppl 1) 4-34
• 5 von Knobloch R, Hegele A, Brandt H. et al . Serum DNA and urine DNA alterations of urinary transitional cell bladder carcinoma detected by fluorescent microsatellite analysis.  Int J Cancer. 2001;  94 67-72
• 6 Shariat S F, Matsumoto K, Casella R. et al . Urinary levels of soluble e-cadherin in the detection of transitional cell carcinoma of the urinary bladder.  Eur Urol. 2005;  48 69-76
• 7 Zhao H, Grossman H B, Delclos G L. et al . Increased plasma levels of angiogenin and the risk of bladder carcinoma: from initiation to recurrence.  Cancer. 2005;  104 30-35
• 8 Danen E H. Integrins: regulators of tissue function and cancer progression.  Curr Pharm Des. 2005;  11 881-891
• 9 von Bredow D C, Nagle R B, Bowden G T. et al . Degradation of fibronectin fibrils by matrilysin and characterization of the degradation products.  Exp Cell Res. 1995;  221 83-91
• 10 Risteli J, Risteli L. Analysing connective tissue metabolites in human serum. Biochemical, physiological and methodological aspects.  J Hepatol. 1995;  22 77-81
• 11 Warawdekar U M, Zingde S M, Iyer K S. et al . Elevated levels and fragmented nature of cellular fibronectin in the plasma of gastrointestinal and head and neck cancer patients.  Clin Chim Acta. 2006;  DOI: 10.1016/j.cca.2006.03.023
• 12 Akiyama S K, Olden K, Yamada K M. Fibronectin and integrins in invasion and metastasis.  Cancer Metastasis Rev. 1995;  14 173-89
• 13 Zaher A, Sheridan T. Tumor markers in the detection of recurrent transitional cell carcinoma of the bladder: a brief review.  Acta Cytol. 2001;  45 575-581
• 14 Kirkali G, Tuzel E, Guler C. et al . Significance of tissue laminin P(1) elastase and fibronectin levels in transitional cell carcinoma of the bladder.  Eur Urol. 2001;  39 292-299
• 15 Hegele A, Heidenreich A, Varga Z. et al . Cellular fibronectin in patients with transitional cell carcinoma of the bladder.  Urol Res. 2003;  30 363-366
• 16 Kropf J, Gressner A M. Two sensitive time-resolved fluoroimmunoassays for cellular fibronectin.  Clin Chem. 1995;  41 1283-1287
• 17 Wittekind C, Meyer H J, Bootz F. TNM-Klassifikation maligner Tumoren. Berlin; Springer Verlag 2003
• 18 Humphries M J, Obara M, Olden K. et al . Role of fibronectin in adhesion, migration, and metastasis.  Cancer Invest. 1989;  7 373-393
• 19 Ioachim E, Michael M, Stavropoulos N E. et al . A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma.  BJU Int. 2005;  95 655-659
• 20 Menendez V, Fernandez-Suarez A, Galan J A. et al . Diagnosis of bladder cancer by analysis of urinary fibronectin.  Urology. 2005;  65 284-289
• 21 Castellani P, Siri A, Rosellini C. et al . Transformed human cells release different fibronectin variants than do normal cells.  J Cell Biol. 1986;  103 1671-1677