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Study of p53 and Ki-67 markers in patients operated by urinary bladder carcinoma in Botucatu Medical College Hospital, from 1980 to 2000: correlation of clinical and survival data with immunohistochemical findings obtained with tissue micro array

Grant number: 11/11537-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2012
Effective date (End): June 30, 2013
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Flávio de Oliveira Lima
Grantee:Leonardo Ribeiro Nascimento
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Urological neoplasms are a frequent cause of morbidity and mortality in Western populations, with high frequency in Brazil, marked in the South and Southeast. Urothelial bladder tumors, which have as one of its most striking features of a relatively high rate of recurrence and progression to invasiveness of surrounding tissues, are a rich natural model for studying carcinogenesis. Although 70% of transitional cell carcinomas are not invasive initially, tend to progress rapidly if not properly treated. Of these, approximately 15% progress to invasive cancer. Over 70% of so-called superficial urothelial tumors recur after resection, and involvement of the muscular wall of the bladder implies a worse prognosis, requiring aggressive surgical intervention, for example, radical cystectomy. There is need for sensitive markers, specific and low morbidity, allowing both the early detection of bladder cancer as the estimate of the probability of progression. Research in molecular biology have allowed the identification of changes in different proto-oncogenes and tumor suppressor genes, which in various combinations contribute to the development of tumors. Among the markers, we can highlight the p53 and Ki-67. The strong association of p53 protein overexpression with a higher rate of progression and recurrence of bladder cancer has been demonstrated, with up to 40% of bladder tumors with mutated TP53. The analysis of this gene may provide valuable information regarding the progression and recurrence of tumors. Deletions or mutations of the TP53 gene have been associated with increased aggressiveness of bladder carcinoma in situ or invasive, suggesting the performance of a central role in the development of malignant disease, and many studies associate their overexpression with poor prognosis. Another important marker of bladder carcinoma, subject of much research, the corresponding Ki-67 antibody which recognizes an antigen that is associated to the cell nucleus and which continuously ciclizantes cells, is expressed at all stages of the cell cycle, except in G0. Some studies have shown the superiority of Ki-67 as a marker of cell proliferation, not to suffer so many influences from internal and external factors. Moreover, its nuclear expression in a defined period of the cell cycle may represent an advantage over its use as a biological marker. The use of the TMA block has multiple advantages over traditional cutting, including: great economy of reagents and time to perform the reactions, the reactions uniformity and ease in the interpretation of comparative cases in the research; possibility of repeating the reactions multilevel block, simplifying the task of research lines for the use of the block in more than one project. In the last decade, the contribution of large volumes of information about the molecular aspects of urothelial neoplasms has led to changes in classification that now seeks to integrate its morphological features with the biological behavior and genetic characteristics. This accumulation of knowledge was obtained by using various techniques to exploit genomics, and cytogenetics, fluorescent in situ hybridization (FISH), comparative genomic hybridization (CGH), assessment of loss of heterozygosity (LOH) and microsatellite instability analysis. Recent advances in the field of Molecular Biology, Genomics and Proteomics of have used as a source of study materials, fresh or frozen tissue, is considered the formaldehyde fixation and paraffin embedding as a serious limitation to its use, until recently restricted the technique of immunohistochemistry. But it is routinely used in the world, and tissue storage file is cheap, easy, and associated information from medical records.

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