Quantitation of AgNORs in urothelial cancer - evaluation of diagnostic parameters in histology and cytology
Abstract
The value of morphometry of silver stained nucleolar organizer regions (AgNOR) was assessed in 80 consecutive patients which had a diagnostic bladder washout prior to subsequent transurethral biopsy or tumor resection. 47 cases had transitional cell cancer, 12 flat atypical bladder lesions currently free of tumor cystoscopically. 19 patients without history of bladder carcinoma and histologically no epithelial atypia served as normal controls. In tissue sections urothelium exhibiting no or mild dysplasia showed few but large AgNORs (mean number [MNN]=3.4±0.5, mean area [MNA]=0.29±0.08μm2). Flat atypical epithelium with moderate or severe dysplasia (D2, Cis), as well as, carcinoma displayed numerous silver stained dots (MNN=6.4±1.4; MNA=0.12±0.04μm2). Regression analysis revealed an inverse correlation between MNN and MNA (r=0.67, p<0.001). Using the quotient of both parameters (NQ=MNN/MNA) transitional cell bladder lesions could be subdivided into urothelium i.) with no or mild dysplasia (normal), ii.) exhibiting moderate dysplasia (D2) or low grade carcinoma (G1), and iii.) displaying severe dysplasia (Cis) or high grade carcinoma (G2,G3). Identical diagnostic groups could be separated in the cytological specimens by determination of the mean total AgNOR area (TNA) in 30 most atypical cells. Thereby, the quotient of TNA in atypical and TNA in normal urothelial cells (AgNOR-index) proved to be the most sensitive parameter in detecting malignancy in urinary cytology.