Evaluation of Cellular Fibronectin Plasma Levels as a Useful Staging Tool in Different Stages of Transitional Cell Carcinoma of the Bladder and Renal Cell Carcinoma

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Abstract
Reliable markers for both renal cell carcinoma (RCC) and transitional cell carcinoma of the bladder (TCC) are lacking. During tumor progression and invasion components of extracellular matrix (ECM) are degraded and parts of these different components are detectable in plasma. Cellular fibronectin (cFN) represents a well characterized ECM protein. In contrast to fibronectin in plasma produced by hepatocytes (FN) cFN has a total extra domain sequence and occurs in much smaller amounts in the circulation. The aim of our study was to evaluate cFN as a marker and to determine its possible role in clinical staging of TCC and RCC. Blood samples were collected from 30 patients before they underwent transurethral resection of the bladder because of newly diagnosed TCC. Additionally samples were collected from 69 patients with RCC before therapy. Sixty patients with non-malignant urological disorders were recruited as control group. Determination of cFN in plasma was performed by using a highly sensitive time-resolved fluorescence immunoassay (TRFIA). The control group had median cFN plasma levels of 437 ng/ml. Patients suffering from TCC or RCC showed significantly higher cFN levels. In patients with muscle invasive TCC significant higher cFN levels (p < 0.05) could be demonstrated compared to non-muscle invasive TCC. Similar results were found in RCC with significant elevated cFN levels in metastatic RCC (p < 0.005) compared to localized stage of disease. No differences were found concerning tumor grading in both malignancies. In the face of significant elevated cFN levels in TCC and RCC our data underline the important role of cFN. For future investigations the elevated cFN levels in locally progressed and metastastic disease, indicating a clinically useful tool for preoperative staging and postoperative monitoring, are of high interest.

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