Expression of CUL1 correlates with tumour‐grade and recurrence in urothelial carcinoma

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Excerpt

Urothelial carcinoma (UC) is the second most common genitourinary malignancy and the ninth most common cancer in the world.1 The majority of UC tumours are found in the urinary bladder, and while upper urinary tract (ureter or renal pelvis) UC accounts for 5–10% of all worldwide cases.2 Urothelial bladder cancer (UBC) is a frequently occurring malignancy of the urinary tract. Natural history and tumour biology of UBC have been studied extensively and are relatively well defined.3 Recurrence of the disease occurs in about 70% of patients, among which 10 to 30% have progression in grade and stage.4 Traditional surgical removal of the tumour via either transurethral resection or removal of the whole bladder (radical cystoprostatectomy) has been the standard treatment for these patients and has played a role in lowering recurrence rates or maintaining quality of life. Therefore, reliable predictive and prognostic markers are required to distinguish indolent from aggressive metastatic UBC for proper clinical management of the patients.
The cullin family of proteins was first identified in 1996 as being required for cell cycle exit in Caenorhabditis elegans5 and for the G1‐to‐S‐phase transition in budding yeast.6 Members of the cullin family (Cullin‐1, Cullin‐2, Cullin‐3, Cullin‐4A, Cullin‐4B, Cullin‐5, Cullin‐7, PARC and APC2) provide the scaffold of Cullin‐Ring Ligase (CRL) complexes responsible for a large portion of ubiquitin‐proteasome system (UPS)‐mediated proteolysis. The family members are characterized by an evolutionarily conserved cullin‐homology domain, and serve as molecular scaffolds to facilitate the assembly of multimeric CRLs. Cullin‐1 (CUL1) is the most extensively characterized member of the cullin family and a key component of SCF E3s, which are composed of four proteins, cullin1/Cdc53, Rbx1/Roc1/Hrt1, Skp1 and an F‐box protein, and has an indispensable role in both cell cycle progression and early embryogenesis.
The use of molecular markers for characterization of UBC allows improved and a more complete insight in the nature of cancer than use of histologic evaluation alone. The aim of this research was to further clarify the relationship between CUL1 expression and biological behaviour of UBC and the clinical outcome of the disease. We examined the expression of CUL1 in 132 UBCs using immunohistochemistry, and correlated the results with clinicopathological factors of the disease.
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