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

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.

Fig. 1

Long-term survival of surgically treated RCC patients in correlation with bFGF expression within the primary tumour specimens. Classification of patients into two groups according to a cut-off value of 5% for the relative amount of tumour cells stained positively for bFGF. Difference between both groups not statistically significant (P=0.42)

Fig. 2

Long-term survival of surgically treated RCC patients in correlation with bFGF expression within the invasive front tissue. Classification of patients into two groups according to a cut-off value of 5% for the relative amount of tumour cells stained positively for bFGF. Difference between both groups statistically significant (P=0.03)

Fig. 3

Positive immunohistochemical staining in renal parenchyma (a) and RCC (b), 160×

Fig. 4

Positive immunohistochemical staining in renal parenchyma (a) and RCC (b), 400×