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A bench marker detects cancer

A protein can identify bladder cancer in a urine test with precision

With the goal of finding out at the very moment of diagnosis what the evolution of the illness in each patient will be – which would simplify the choice of treatment – the urologist Dr. Marco Aurélio Silva Lipay, of the Federal University of São Paulo (Unifesp), studied the glycoprotein CD44 as a marker molecule for cancer of the bladder. A substance which participates in the structuring of the tissues and one f the membranes of the cells, like cement in a wall, it is already used in the diagnosis of cancer of the kidney and of the breast.

According to Dr. Lipay, whose study was financed by FAPESP, bladder cancer is the fourth most common in the United States; where close to 50,000 new cases are diagnosed a year. In Brazil, the official estimate was 7,550 new cases in 1999, “but it may be underestimated”. When the glycoprotein CD44 is not present in the tissue, it is a sign of disorganization in the tissue’s structure, and that the cells are beginning to disintegrate in a disordered manner. As cancer is an illness of disordered multiplication of cells, it is presumed that the lack of an integrating element such as CD44, points to a bad prognosis, as the degree of aggressiveness of the cancer is directly related to the production of metastasis cells that break away from the original tumor.

Still in an experimental phase, the CD44 method depends on a biopsy – a removal of a sample of the infected region for analysis. Dr. Lipay intends to increase the sensitivity of the test and turn it non-invasive, detecting the presence or absence of CD44 in the urine. After the collection of the urine, centrifuging takes place to obtain the cells that have come off the internal mucus of the bladder. The RNA (ribonucleic acid) of these cells is extracted and enlarged for reaction in a polymer chain. If the CD44 is present, the RNA that promotes its production will also be enlarged for reaction.

Genetic alterations
Dr. Lipay states that the gene which codifies the glycoprotein CD44 is mapped on the short arm of chromosome 11. “There are other markers of the bladder tumor under study. The ideal would be for us to have a single marker.” The cancer of the bladder generally begins in the mucus and, at the moment of diagnosis, it is impossible to know if the patient will be cured or not. “Cancer is a genetic illness at the somatic level: or that is, before the illness shows itself, the cells pass through various steps of molecular alterations.”, he explains.

The geneticist Dr. Monica Vanucci Nunes Lipay, who guided the project together with the urologist Dr. Flavio Hering, both from Unifesp, adds: “Genetic factors, such as tobacco use, could interfere in the process, making the alterations easier. Cancer is an illness of multiple steps. If an individual has a genetic alteration that indicates a tendency to develop the illness but was not exposed to the aggressive agents, it may well be that the person will never develop the cancer.”

Dr. Lipay will continue on his line of research towards the creation of a pool of markers for tumors that represent the real situation of the patient.

The Project
Study of the Standard Presence of Glycoprotein CD44, by Immunohistochemistry Technique as a Prognostic Factor in Urothelial Neoplasty of the Bladder (nº 99/01289-5); Modality Aid to a research project; Coordinator Dr. Flávio Luiz Ortiz Hering – Unifesp; Investment R$ 36,043.75