Transitional cell carcinoma (TCC) of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer. 1. Background Transitional cell carcinoma (TCC) represents more than 90% of bladder cancers [1], ranking among genitourinary malignancies only behind prostate cancer for frequency and estimated mortality. At initial diagnosis, more than 70% of bladder tumors are confined to the mucosa or lamina propria. Transurethral resection of nonmuscle invasive tumors can be accompanied by intrabladder therapy, depending on tumor depth and grade. However, more then 70% of patients can present tumor recurrences after treatment, with up to 30% of patients progressing to higher tumor stage and grade [2]. In this view, close and accurate disease surveillance is essential for monitoring tumour recurrence and progression to invasive disease. The current standard diagnostic iter includes urine cytology, imaging, and flexible cystoscopy. Cytology represents the cornerstone of urine-based bladder cancer diagnosis. It involves microscopic examination of precancerous and cancerous cells present in the urine by a pathologist. Although its high specificity (96%), the sensitivity is lower (44%) [3], particularly for low-grade tumors [4]. Quanticyt is a karyometric of bladder washing for the quantitative grading of urine cytology [5]. Based on the DNA content levels and nuclear morphometry, bladder cancer can be classified into low, intermediate, and high risk of recurrence [6]. Emerging data from the main studies involving the use of Quanticyt showed that this test has a sensitivity of 56.4% (range 42.1–69%) and a specificity of 72.1% (range 67.9–76%) [7, 8]. The use of cystoscopy has been successful in monitoring bladder cancer recurrence [9].
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