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Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels

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Abstract

The prognostic value of bFGF for surgically treated renal cell cancer (RCC) patients was evaluated by immunohistochemistry (IHC) and the tissue microarray technique (TMA). Additionally, preoperative serum bFGF levels were correlated to tumour stage and the presence of metastases at initial diagnosis. Serum levels of bFGF were measured by ELISA in 39 healthy volunteers, in 37 patients with benign urologic diseases and in 74 RCC patients, 26 of whom revealed lymph node or distant metastases. bFGF expression as detected by IHC was investigated in 777 tissue cores from 259 different RCC patients [median follow-up: 138 (36–240) months]. Eighty eight patients died from tumour progression. For each patient, the TMA slides contained a tissue core from the primary tumour, its invasion front and the normal renal parenchyma. bFGF serum levels were higher in RCC patients vs healthy volunteers (P<0.01) and vs patients with benign urologic diseases (P<0.01). Metastasized patients revealed higher bFGF serum levels than organ-confined specimens (P<0.01). As detected by IHC only increased bFGF expression in the invasion front tissue correlated with the patients’ long-term survival (log rank test) (P=0.03). In multivariate analysis regional LN metastases (P<0.01), the histological grading (P<0.01), and an increased bFGF expression in the invasion front (P=0.04) independently predicted the patients’ clinical prognosis. Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas. The value of bFGF serum levels as indicators of systemic tumour dissemination remains to be determined.

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References

  • Bichler KH, Wechsel HW (1999) The problematic nature of metastasized renal cell carcinoma. Anticancer Res 19:1463–1466

    PubMed  CAS  Google Scholar 

  • Chodak GW, Hospelhorn V, Judge SM, Mayforth R, Koeppen H, Sasse J (1988) Increased levels of fibroblast growth factor-like activity in urine from patients with bladder or kidney cancer. Cancer Res 48(8):2083–2088

    PubMed  CAS  Google Scholar 

  • Cronauer MV, Schulz WA, Seifert HH, Ackermann R, Burchardt M (2003) Fibroblast growth factors and their receptors in urological cancers: basic research and clinical implications. Eur Urol 43:309–319

    Article  PubMed  CAS  Google Scholar 

  • Dosquet C, Coudert MC, Lepage E, Cabane J, Richard F (1997) Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? Clin Cancer Res 3:2451–2458

    PubMed  CAS  Google Scholar 

  • Duensing S, Grosse J, Atzpodien J (1995) Increased serum levels of basic fibroblast growth factor (bFGF) are associated with progressive lung metastases in advanced renal cell carcinoma patients. Anticancer Res 15:2331–2333

    PubMed  CAS  Google Scholar 

  • Edgren M, Lennernas B, Larsson A, Nilsson S (1999) Serum concentrations of VEGF and b-FGF in renal cell, prostate and urinary bladder carcinomas. Anticancer Res 19:869–873

    PubMed  CAS  Google Scholar 

  • Emoto N, Isozaki O, Ohmura E, Ito F, Tsushima T, Shizume K, Demura H, Toma H (1994) Basic fibroblast growth factor (FGF-2) in renal cell carcinoma, which is indistinguishable from that in normal kidney, is involved in renal cell carcinoma growth. J Urol 152:1626–1631

    PubMed  CAS  Google Scholar 

  • Ferrara N (2000) Vascular endothelial growth factor and the regulation of angiogenesis (see discussion pp 35–36). Recent Prog Horm Res 55:15–35

    PubMed  CAS  Google Scholar 

  • Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    Article  PubMed  CAS  Google Scholar 

  • Fujimoto K, Ichimori Y, Yamaguchi H, Arai K, Futami T, Ozono S, Hirao Y, Kakizoe T, Terada M, Okajima E (1995) Basic fibroblast growth factor as a candidate tumor marker for renal cell carcinoma. Jpn J Cancer Res 86:182–186

    PubMed  CAS  Google Scholar 

  • Godley PA, Ataga KI (2000) Renal cell carcinoma. Curr Opin Oncol 12:260–264

    Article  PubMed  CAS  Google Scholar 

  • Hartmann JT, Bokemeyer C (1999) Chemotherapy for renal cell carcinoma. Anticancer Res 19:1541–1543

    PubMed  CAS  Google Scholar 

  • Izawa JI, Dinney CP (2001) The role of angiogenesis in prostate and other urologic cancers: a review. CMAJ 164:662–670

    PubMed  CAS  Google Scholar 

  • Jacobsen J, Rasmuson T, Grankvist K, Ljungberg B (2000) Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol 163:343–347

    Article  PubMed  CAS  Google Scholar 

  • Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ (2003) Cancer statistics. CA Cancer J Clin 53:5–26

    Article  PubMed  Google Scholar 

  • Karumanchi SA, Merchan J, Sukhatme VP (2002) Renal cancer: molecular mechanisms and newer therapeutic options. Curr Opin Nephrol Hypertens 11:37–42

    Article  PubMed  Google Scholar 

  • Kuczyk MA, Bokemeyer C, Hartmann J, Schubach J, Walter C, Machtens S, Knuchel R, Kollmannsberger C, Jonas U, Serth J (2001) Predictive value of altered p27Kip1 and p21WAF/Cip1 protein expression for the clinical prognosis of patients with localized prostate cancer. Oncol Rep 8(6):1401–1407

    PubMed  CAS  Google Scholar 

  • Mejean A, Oudard S, Thiounn N (2003) Prognostic factors of renal cell carcinoma. J Urol 169:821–827

    Article  PubMed  Google Scholar 

  • Ornitz DM, Itoh N (2001) Fibroblast growth factors. Genome Biol 2 (REVIEWS3005)

  • Pantuck AJ, Belldegrun AS, Figlin RA (2001a) Nephrectomy and interleukin-2 for metastatic renal-cell carcinoma. N Engl J Med 345:1711–1712

    Article  PubMed  CAS  Google Scholar 

  • Pantuck AJ, Zisman A, Belldegrun AS (2001b) The changing natural history of renal cell carcinoma. J Urol 166:1611–1623

    Article  PubMed  CAS  Google Scholar 

  • Pantuck AJ, Zeng G, Belldegrun AS, Figlin RA (2003) Pathobiology, prognosis, and targeted therapy for renal cell carcinoma: exploiting the hypoxia-induced pathway. Clin Cancer Res 9:4641–4652

    PubMed  CAS  Google Scholar 

  • Poon RT, Fan ST, Wong J (2001) Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 19:1207–1225

    PubMed  CAS  Google Scholar 

  • Powers CJ, McLeskey SW, Wellstein A (2000) Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 7:165–197

    Article  PubMed  CAS  Google Scholar 

  • Rasmuson T, Grankvist K, Jacobsen J, Ljungberg B (2001) Impact of serum basic fibroblast growth factor on prognosis in human renal cellcarcinoma. Eur J Cancer 37(17):2199–2203

    Article  PubMed  CAS  Google Scholar 

  • Singh RK, Bucana CD, Gutman M, Fan D, Wilson MR, Fidler IJ (1994) Organ site-dependent expression of basic fibroblast growth factor in human renal cell carcinoma cells. Am J Pathol 145:365–374

    PubMed  CAS  Google Scholar 

  • Slaton JW, Inoue K, Perrotte P, El Naggar AK, Swanson DA, Fidler IJ, Dinney CP (2001) Expression levels of genes that regulate metastasis and angiogenesis correlate with advanced pathological stage of renal cell carcinoma. Am J Pathol 158:735–743

    PubMed  CAS  Google Scholar 

  • Strohmeyer D (1999) Pathophysiology of tumor angiogenesis and its relevance in renal cell cancer. Anticancer Res 19:1557–1561

    PubMed  CAS  Google Scholar 

  • Sweeney JP, Thornhill JA, Graiger R, McDermott TE, Butler MR (1996) Incidentally detected renal cell carcinoma: pathological features, survival trends and implications for treatment. Br J Urol 78:351–353

    PubMed  CAS  Google Scholar 

  • Wechsel HW, Bichler KH, Feil G, Loeser W, Lahme S, Petri E (1999) Renal cell carcinoma: relevance of angiogenetic factors. Anticancer Res 19:1537–1540

    PubMed  CAS  Google Scholar 

  • Wechsel HW, Feil G, Bichler KH, Beiter T, Gleichmann R (2000) Serologic angiogenesis factors and microvascular density in renal cell carcinoma: two independent parameters. Anticancer Res 20:5117–5120

    PubMed  CAS  Google Scholar 

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Acknowledgements

The present investigation was supported by a grant from the Eberhard Karls University Tübingen (Fortüne Program: MK 1332-1-0) and the Sanofi-Aventis Group.

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Authors and Affiliations

  1. Department of Urology, Eberhard Karls University Tübingen, Hoppe-Seyler Str. 3, 72076, Tübingen, Germany

    M. Horstmann, A. S. Merseburger, G. Feil, J. Hennenlotter, U. Nagele, A. Anastasiadis, A. Stenzl & M. Kuczyk

  2. Department of Urology, Hannover University Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany

    E. von der. Heyde & J. Serth

  3. Department of Pathology, Hannover University Medical School, Carl-Neuberg Str. 1, 30625, Hannover, FRG

    G. Wegener

  4. Department of Clinical Cancer Registry, Hannover University Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany

    M. Mengel

  5. Department of Haematology/Oncology, University Hospital Eppendorf, University of Hamburg, Martinistrasse 52, 20246, Hamburg, Germany

    C. Bokemeyer

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  1. M. Horstmann
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  2. A. S. Merseburger
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  3. E. von der. Heyde
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  4. J. Serth
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  5. G. Wegener
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  6. M. Mengel
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  7. G. Feil
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  8. J. Hennenlotter
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  9. U. Nagele
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  10. A. Anastasiadis
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  11. C. Bokemeyer
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  12. A. Stenzl
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  13. M. Kuczyk
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Correspondence to M. Kuczyk.

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Horstmann, M., Merseburger, A.S., Heyde, E.v.d. et al. Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels. J Cancer Res Clin Oncol 131, 715–722 (2005). https://doi.org/10.1007/s00432-005-0019-y

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  • DOI: https://doi.org/10.1007/s00432-005-0019-y

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