A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer.

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.

Correlation between p53 mutations and HPV in bilharzial bladder cancer.

Alterations of the p53 tumor suppressor gene are the most common genetic changes detected in human cancers as well as in papillary and invasive bladder cancer. Several studies have demonstrated an association between HPV infection and urological malignancies. In the present work, the p53 gene status was studied together with the frequency of HPV in 99 cases of Bilharzial bladder cancer [BBC] in Egypt and both were correlated to the clinicopathological features of the patients. SSCP and sequencing were used to screen the p53 gene for mutations at exons 4-10 and IHC was performed to detect protein overexpression. PCR was used for detection and typing of HPV-DNA in tumor samples. p53 mutations were detected in 33.3% of the studied cases whereas protein overexpression was detected in 35.6% of the cases. The highest concordance rate was observed in cases harboring mutations at exon 4 [87.5%]. Bilharzial infestation was obvious in 72.2% of the cases that showed mutations. Exon 8 showed the highest rate of mutation [32%] followed by exons 4 and 5 [22% each]. The commonest mutational event was G:C transversion [15/50] especially at CpG dinucleotides. A mutational hot spot was detected at exon 4, codons 72-73. HPV-DNA was detected in 48.97% of the cases the majority of which [64.6%] were of type 16. Significant correlation was found between p53 mutation and the pathological stage as well as p53 overexpression and tumor grade. Our results demonstrate that the mutational spectrum in BBC is different from that of bladder cancer in Western countries in many aspects and suggest an etiological role of HPV in this type of neoplasm. However, both HPV infection and p53 gene abnormalities may contribute to Bilharzial bladder carcinogenesis in an independent way.