Epidermal growth factor receptor mRNA expression in peripheral blood of bladder cancer patients: a potential marker to detect treatment failure.

Recent clinical trials have demonstrated how, despite radical surgery and adjuvant chemotherapy, more than half of muscle invasive bladder cancers develops hematogenous spread and distant metastases. Furthermore, a high percentage of patients with superficial disease has progression to higher stage tumors, which is difficult to predict on the basis of clinical features (1). In a recent report by Gazzaniga et al. (2), we investigated the utility of an EGFR-based RT-PCR assay to detect circulating cancer cells in the peripheral blood collected before surgery from a subset of bladder cancer patients. The finding of EGFR mRNA in blood drawings performed in nonmetastatic patients who relapsed early lead us to the hypothesis of the utility of such an assay in the pre-surgical staging of bladder cancer patients. In the period after the publication of the article, we sought to investigate whether EGFR mRNA expression was modified in blood samples collected from the same patients 3 months after surgery and from patients with locally advanced tumors 1 year after chemotherapy. RNA extraction from whole blood and RT-PCR with EGFR-specific primer sequences were performed as described previously (2). The results of EGFR amplification in blood samples collected after surgery and after adjuvant therapy were then compared with that obtained in the same patients before surgical treatment. The comparative analysis between EGFR amplifications in blood samples collected before and after surgical treatment revealed that EGFR mRNA expression was invariable in all patients except 2, who were EGFR negative before transurethral resection and resulted EGFR positive 3 months later. Follow-up data revealed in both these patients a progression of disease, as shown in Table 1. In most patients with higher staged tumors, who had shown high EGFR expression levels in blood before surgery, we observed the absence of EGFR-specific amplifications in blood drawings performed 1 year after adjuvant cisplatinum-based chemotherapy. All these patients are at present in stability of disease. In 2 of these metastatic patients, however, EGFR mRNA expression in blood samples collected before and after therapy remained invariable; both these patients died because of the disease (Fig. 1). These results may represent an additional confirmation to the utility of EGFR-based RT-PCR assay in monitoring patients with bladder cancer also in a postsurgical phase, as