ABSTRACT
The aim of this study was to assess patterns of CCND3 gene amplification in bladder cancer and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 102 primary bladder tumor samples in which there was enough tissue material to assess CCND3 gene status by fluorescent in situ hybridization (FISH) was the study group. CCND3 gene FISH amplification present in 31.4 percent of bladder carcinomas, was related to tumor progression (p=0.021) and lower time to progression (mean+-SD; 25.75+-15.25 months) as compared to 33.29+-11.0 months in the CCND3 not amplified group (p=0.05). By immunohistochemistry, Cyclin D3 labeling index was higher in the CCND3 amplified group (mean+-SD, 76.69+-27.51) than in not amplified (mean+-SD, 21.57+-7.02) (p less than 0.0001). The univariate survival analysis showed CCND3 gene amplification to be associated to a shorter progression-free survival (p=0.020) together with WHO histological grade (p=0.001) and pT stage category (p less than 0.0001). Coxs regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p= 0.030, RR3.561, 95 percent CI 1.128-11.236) together with pT category (p less than 0.0001, RR5.834, 95 percent CI 2.364-14.395). Our FISH analysis suggests that CCND3 gene amplification is a marker of aggressiveness and might be a predictor of tumor progression in bladder urothelial carcinoma.
Subject(s)
Biomarkers, Tumor/genetics , Cyclin D3/genetics , In Situ Hybridization, Fluorescence/methods , Urinary Bladder Neoplasms/genetics , Aged , Disease Progression , Female , Humans , Male , Middle Aged , Urinary Bladder Neoplasms/mortalityABSTRACT
Two cases of intestinal-type adenocarcinoma of the renal pelvis (ARP) in 48- and 63-year-old females are presented. Both had a previous history of urinary obstructive disease, one secondary to staghorn calculus and the other to postirradiation stenosis following treatment for carcinoma of the cervix. Immunohistochemical findings revealed marked positivity to epithelial membrane antigen and focal positivity to cytokeratins and carcinoembryonic antigen. Chronic irritation of the renal pelvis plays an important role in the pathogenesis of ARP. In one of our cases of multicentric origin, the synergistic effect of pelvic irradiation and cyclophosphamide chemotherapy in a patient with a previous squamous cell carcinoma of the cervix, may be responsible for the pathogenesis of the ARP.
