ABSTRACT
OBJECTIVE: We investigated the expression of thymidine phosphorylase (TP) in bladder carcinomas and assessed its prognostic significance in superficial bladder cancer samples. PATIENTS AND METHODS: We studied 142 primary bladder cancer samples immunohistochemically for nuclear thymidine phosphorylase (TPN), cytoplasmic (TPC) and stromal (TPSTR) expression. We correlated them with standard clinicopathological features (grade, stage, concurrent in situ, multiplicity, primary or recurrent status), as well with recurrence and progression. We examined also the relationship between TP and tumor microvessel density. RESULTS: The level of all types of TP correlated well with stage, while grade correlated well only with TPSTR and the presence of carcinoma in situ only with TPN. Patients with low levels of TPN had a longer tumor free interval, during a 38.6 months mean follow up time. Regarding the association between TP count and microvessel density we found the strongest association with TPSTR (p=0.003), a borderline statistical significance with TPC (p=0.049) and no relationship with TPN (p=0.072). CONCLUSIONS: We suggest that the assessment of TPN might be useful for predicting recurrence in superficial bladder cancer. We propose also that TP may stimulate angiogenesis.
Subject(s)
Carcinoma, Transitional Cell/metabolism , Thymidine Phosphorylase/metabolism , Urinary Bladder Neoplasms/metabolism , Aged , Carcinoma, Transitional Cell/pathology , Cell Nucleus/metabolism , Cytoplasm/metabolism , Disease Progression , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVE: To assess the prognostic significance of angiogenesis parameters such as microvessel density (MVD) and vascular endothelial growth factor (VEGF) in superficial bladder cancer. PATIENTS AND METHODS: We studied 127 superficial bladder cancer samples immunohistochemically for the above factors. We compared them with standard clinicopathological features (grade, stage, concurrent in situ, multifocality, primary or recurrent status) as well as with p53 expression, recurrence and progression to muscle infiltrating disease. RESULTS: During a 36 months median follow up of 109 patients with superficial primary tumors (min. 3, max. 69 months), 80 of them recurred (73.4%), while 8 patients (7.3%) progressed to muscle invading disease. A significant correlation was noted between MVD and VEGF in all 127 samples (p = 0.019). No association was noted between MVD or VEGF with the other clinicopathological features, recurrence or progression. Although progression free survival rates of categorized microvessel density (up to and higher than median value) differed significantly only in grade 3 patients, no independent prognostic significance could be attributed to MVD. No correlation was observed between MVD or VEGF with p53 protein. CONCLUSIONS: Based on our data we suggest that VEGF is not useful for predicting recurrence or progression in superficial bladder cancer. Microvessel density determination may help to predict progression of grade 3 patients to muscle invasive disease but not as an independent prognostic factor.
Subject(s)
Carcinoma, Transitional Cell/blood supply , Neovascularization, Pathologic/pathology , Urinary Bladder Neoplasms/blood supply , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/chemistry , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Disease Progression , Disease-Free Survival , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Prognosis , Tumor Suppressor Protein p53/analysis , Urinary Bladder Neoplasms/chemistry , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Vascular Endothelial Growth Factor A/analysisABSTRACT
OBJECTIVE: To determine if intravesically administered recombinant interferon (IFN) gamma may serve as adjuvant first line treatment in prophylaxis of superficial bladder cancer by reducing its risk for recurrence, in the short term. MATERIAL AND METHODS: A total of 54 patients (43 males and 11 females) with superficial bladder tumours (Ta/T1) initially treated with transurethral resection for their tumors were randomized into two groups: Twenty-eight patients were left untreated after the transurethral resection (controls) whereas 26 patients received intravesical IFN gamma adjuvantly, at a dosage of 0.7 mg per week for 8 weeks. Patients with G1 tumors and carcinoma in situ were excluded. The follow up had a mean time of 12.1 months. Recurrence or progression, as terminal events of the study, were recorded. The comparison of the recurrences between the two groups was performed by estimating: (a) the simple recurrence rate, and (b) the interval to tumor recurrence in each group. RESULTS: Tumor recurrence was detected in 24 controls (86%) and in 16 (62%) patients of the IFN gamma group (p = 0.043). The comparison of the Kaplan-Meier disease-free survival curves between the two groups of patients indicated that intravesical instillations of IFN gamma exerted a continuous protective effect to those who received the agent, in the follow up period (p = 0.0237). No serious side-effects were noted. CONCLUSIONS: Intravesically administered IFN gamma has a demonstrable protective role as first line adjuvant treatment in superficial bladder cancer. This role is mainly focused on prevention of recurrences in the short term. Further prospective studies with longer follow up are required, in order to define the exact place of the drug in the urologist's armamentarium.
