Clinical Utility ofUrinary Alpha1- Antitrypsin inBladder Cancer Patients

Abstract

Bladder cancer is the most common cancer in developed countries especially Egypt. It is characterized by high recurrence rate and most of the recurred cases may progress to a higher grade and stage. Therefore, long term and close surveillance of patients with bladder cancer is mandatory. The gold standard for diagnosing bladder cancer is cystoscopy. It provides direct visualization and localization of the tumor and a means for biopsying abnormal areas. It also permits initial assessment of tumor grade and stage. However, cystoscopy fails to detect CIS. It may have inconclusive results particularly in case of cystitis. The procedure is invasive, relatively expensive, often a source of patient anxiety, in addition to a 10% possibility of causing urinary tract infection. Another adjuvant means for diagnosis of bladder cancer is urine cytology. However, it has many limitations, namely that well-differentiated tumors have normally appearing cells, are tightly cohesive and not readily shed in urine. This makes its overall sensitivity among different grades of differentiation only 20% to 40%. These concerns have driven the search for other non-invasive, less expensive and more reliable markers for this disease. Among these is A1AT is a protease inhibitor belongs to the serpin superfamily; located on chromosome 14q32.1, it plays a major role in the normal physiological processes such as angiogenesis, intravascular fibrinolysis and wound healing. However, it may also participate in pathological conditions such as tumor invasion and metastasis which require degradation of the basement membrane, stimulation of angiogenesis, and migration. Therefore, its level could reflect tumor burden that may help in cancer detection and monitoring.

In this regard, the aim of this study was to assess the clinical utility of urinary alpha1- antitrypsin as a non- invasive tool for early detection of bladder cancer patients and their prognostic role through their association with different histopathological stages and grades of the disease.a

This study included 50 bladder cancer patients; patients were classified into two groups according to their diagnosis. Group A included newly diagnosed bladder cancer patients before the treatment. Group B included 20 patients with benign renal diseases such as renal stones, bladder stones and cystitis. In addition, Group C included 15 apparently healthy subjects served as a healthy control group.

Our study revealed a highly significant increase of urinary levels of A1AT in bladder cancer patients when compared to both pathological and healthy control subjects. Moreover, urinary levels of A1AT in stage Tawere significantly higher than pathological and healthy control subjects.

As regards the relation between urinary A1AT and muscle invasiveness, urinary A1AT levels were significantly higher in stage T2 (MIBC) than stages Ta and T1 (NMIBC).

As regards the relation between urinary A1AT and bladder cancer grades, our study revealed highly significant increase in urinary A1AT in poorly differentiated tumors when compared to well differentiated tumors.