The Role of Urinary Fibronectin and Telomerase in Patients with Superficial Bladder Cancer after Transurethral Resection Treated with BCG

Objective: Bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN) has been found to play a role in BCG therapy. Although adjuvant BCG has been shown to improve the clinical outcome of superficial bladder cancer (SBC), a significant proportion of patients fail to respond to it. Identification of the subset of patients that are going to develop recurrent disease or stage progression after BCG therapy is very important. Telomerase activity represents a potential tool for tumor detection. The aim of the present study was to give an insight into the diagnostic and prognostic values of the quantitative urinary estimation of both fibronectin (FN) and the catalytic subunit of the complex human telomerase reverse transcriptase [hTERT]) as non invasive tumor markers for early detection of patients with high risk superficial transitional cell carcinoma (TCC) and after trans-urethral resection of bladder tumors (TURBT) that received adjuvant BCG immunotherapy to explore its association with recurrence-free-survival (RFS) or development of invasive disease. Materials and methods: The study was carried out on 10 healthy individuals as a control group (group I) and 20 Egyptian patients with histologically confirmed superficial bladder cancer (group II). Patients were underwent formal TURBT. Morning urine samples were collected from every patient, 1 day before and 2days, two weeks, six weeks, three months, six months and one year after TURBT. Also, morning urine samples were collected from the healthy individuals. Urine samples were used for cytological examination, estimation of fibronectin level using ELISA technique and for the quantitative analysis of hTERT using quantitative real time RTPCR technique. Results: The results showed that urinary fibronectin level and normalized hTERTmRNA were significantly higher in SBC patients before TURBT (group II) versus control group (P<0.001). hTERT-mRNA and urinary fibronectin levels were significantly different in group II before and 2 days after TURBT. Urinary fibronectin and normalized hTERTmRNA were significantly lower 2 weeks and 6 weeks after TURBT than patients group 2 days after TURBT. Both markers were significantly lower in fifteen patients 3 months, 6 months and one year after TURBT when compared with their levels 2 days after TURBT. There was insignificant difference of both markers between the control group and fifteen patient one year Bull. Egypt. Soc. Physiol. Sci. 30 (1) 2010 Abdel Aleem et al. 74 after TURBT. The remaining five patients suffered recurrence of tumor. This approach enabled us to identify cutoff values of urinary fibronectin which characterized by 90% sensitivity and 100% specificity and 93.3% accuracy, and that for urinary normalized hTERT with 85% sensitivity and 80% specificity and 83.3% accuracy. Conclusion: On the basis of these results, it could be concluded that both urinary fibronectin and hTERTmRNA can be considered from the best markers for diagnosing superficial bladder carcinoma. These parameters can be also used to determine the presence of residual tumor load after TURBT; also they can give an insight about the expected response to BCG immunotherapy after TURBT and detect the BCG nonresponder patients. It seems conceivable that these emerging urinebased tests may progressively replace urine cytology and form a reliable adjunct to cystoscopy in the diagnosis and follow up of patients with superficial bladder cancer. Key wards: Bacillus Calmette-Guérin (BCG), Superficial bladder cancer (SBC), Fibronectin (FN), transitional cell carcinoma (TCC), carcinoma in situ (CIS), human telomerase reverse transcriptase (hTERT), transurethral resection of bladder cancer (TURBT)