Recent Aspects in the Diagnosis and Prognosis of Bladder Cancer (original) (raw)

Molecular Aspects of Bladder Cancer

European Urology, 2002

The current pathological and clinical parameters provide important prognostic information, yet still have limited ability to predict the true malignant potential of most bladder tumors. In the last years, investigation of the basic mechanisms involved in carcinogenesis and tumor progression by molecular biology has provided a host of markers which are of potential diagnostic or prognostic value for bladder carcinoma. These markers may serve as tools for early and accurate prediction of tumor recurrence, progression and development of metastases and for prediction of response to therapy. The precise prediction of tumor biological behavior would facilitate treatment selection for patients who may bene®t from radical surgical treatment or adjuvant therapy. We provide a current, comprehensive review of the literature on bladder tumor markers with a special emphasis on their prognostic potential. The literature suggests that currently no single marker is able to accurately predict the clinical course of bladder tumors and thus would serve as a reliable prognosticator. A combination of prognostic markers could predict which super®cial tumors need an aggressive form of therapy and which invasive tumors require adjuvant therapy. Altogether, the most promising markers are, at this point, Ki-67 and p53 expression as well as matrixmetalloproteinase complex and angiogenesis.

Prognostic factors in survival of bladder cancer

Cancer, 1992

Clinical and pathologic data of 36 patients with transitional cell carcinoma of the bladder were investigated to determine the significance on patient survival of these factors: pathologic grade and stage; the immunohistochemistry of eight cell and tumor markers; nuclear DNA flow cytometric parameters; and patient smoking status. The bivariate and multivariate statistical analysis significantly correlated patient survival rates with the immunohistochemical expression of blood group, isoantigens A ( P < O.O5),O(H) (P = 0.001), the oncogene-related protein ORP-p21 (P < 0.05), the pathologic grade and stage ( P = 0.002), and the tumor DNA ploidy (P < 0.05). Smoking status correlated aneuploidy (P < 0.05) and tumor expression of ORP-p21 (P < 0.05) with the patient survival rate. Despite the relatively small number of patients in this study, the results suggest that the clinicopathologic variables are significant factors in survival of bladder cancer. Cancer 1992: 70:799-807.

Epidemiology of urinary bladder cancer: from tumor development to patient’s death

World Journal of Urology, 2007

Urinary bladder cancer (UBC) ranks ninth in worldwide cancer incidence. It is more frequent in men than in women. We review the main established/proposed factors, both environmental and genetic, associated with bladder cancer etiology and prognosis. Data were extracted from previous reviews and original articles identiWed from PubMed searches, reference lists, and book chapters dealing with the reviewed topics. Evaluation and consensus of both the contribution of each factor in bladder cancer burden and the appropriateness of the available evidences was done during an ad hoc meeting held during the 18th Congress of the European Society for Urological Research. Cigarette smoking and speciWc occupational exposures are the main known causes of UBC. Phenacetin, chlornaphazine and cyclophosphamide also increase the risk of bladder cancer. Chronic infection by Schistosoma haematobium is a cause of squamous cell carcinoma of the bladder. NAT2 slow acetylator and GSTM1 null genotypes are associated with an increased risk of this cancer. Vegetables and fresh fruits protect against this tumor. Regarding prognosis, there is little knowledge on the predictive role of environmental exposures and genetic polymorphisms on tumor recurrence and progression and patient's death. Although active tobacco smoking is the most commonly studied factor, no deWnitive conclusion can be drawn from the literature. More research is needed regarding the eVect of complex etiological factors in bladder carcinogenesis. Subgroup analysis according to stage, grade, and molecular features may help in identifying speciWc etiological and prognostic factors involved in diVerent bladder cancer progression pathways.

Diagnosis of bladder cancer with urinary cytology, immunocytology and DNA-image-cytometry

Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology, 2001

DNA-image-cytometry and antibodies directed against the Lewis X- and the 486p 3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for the detection of bladder cancer. Cytology, immunocytology and DNA-image-cytometry were performed in spontaneously voided urine samples and barbotage bladder washings from 71 patients. The DNA content was determined using the CM-1 Cytometer according to the recommendation of the ESCAP Consensus Report on Standardization of DNA-image-cytometry (1995). For immunocytological examination we used the monoclonal anti Lewis X antibody P-12 and antibody 486p 3/12. All patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or transurethral resection was done. Histological findings revealed 31 patients with transitional cell carcinomas of different stages and grades of malignancy. 40 patients had various benign diseases of the urinary bladder. Cytology yielded a sensitivity of 68% and a specificity of 100%. DNA ane...

Bladder Cancer: A Simple Model Becomes Complex

Current Genomics, 2012

Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small noncoding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using "bladder cancer" as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up-or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genomewide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up-or downregulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non-genetic, genetic and epigenetic factors causing extensive gene mis-regulation in malignant cells.