Validation of Biomarkers in patients with Urothelial Bladder Carcinoma

Abstract

INTRODUCTION: Bladder cancer is one of the most common urological cancers. Bladder cancer is generally diagnosed by urethra-cystoscopy, which permits direct imagining of tumours and confirmation by biopsy and pathological analysis. Nevertheless, Cystoscopy and voided urine cytology are effective diagnostic methods for investigation of superficial bladder cancer. Flexible cystoscopy being a minimally invasive procedure and has made flexible cystoscopy more acceptable to patients. Voided urine cytology remains the method of choice for the non-invasive detection of bladder cancer, yet whilst it has a specificity of 93%, its sensitivity is only 25-40%, especially for low-grade and T-stage tumours. The clinical spectrum at present can be divided into those with (i) non-muscle invasive bladder cancer, (ii) muscle-invasive bladder cancer, and (iii) metastatic disease. The muscle invasive bladder cancer has a high recurrence rate of 50- 70% as it reoccurs despite conservative measures such as transurethral resection of bladder tumor (TURBT) and intravesical therapy. A wide range of alternative procedures and markers have been proposed and studied for the detection of recurrent bladder tumours. These include 5Aminolevulinic Acid (5-ALA) cytology, nuclear matrix protein 22 (NMP22), BTA test etc. The principle behind 5-ALA fluorescence cytology is based on the metabolism of heme biosynthesis. 5-ALA being the precursor of heme metabolism will selectively get accumulated as protoporphyrin IX (PPIX) in tumor cells. For quantitative analysis, FDA approved commercial test were used which follows the principle of enzyme linked immunoassay. First test includes NMP-22, it is a nuclear mitotic apparatus protein present in the nuclear matrix of all cell type, located in the mitotic spindle during mitosis and is involved in the proper supply of chromatin to daughter. Similarly, BTA has been identified as a human complement factor H related protein (hCFHrp), which is produced by bladder tumour cells in cell cultures and not by any other epithelial cell lines. The present study aimed to detect urothelial bladder carcinoma using 5- ALA and its comparison with conventional cytology, NMP-22 and BTA TRAK quantitative test to estimate activity in the urine of the patients with bladder cancer in a trial to assess their value in the detection of the tumours and to find a reliable non-invasive technique for the diagnosis of cancer bladder. Sensitivity and specificity of these tumour markers was compared to conventional cytology in bladder cancer.