Novel Tissue, Blood and Urine Tests for Prostate Cancer - More Specific than PSA Test

9 Aug 2005 -- Methods for early detection of cancer and for detecting recurrence after primary therapy should be simple and reliable. In the case of prostate cancer, prostate biopsy tissue and blood tests for Calgranulin B, the S100A9 protein, appear to be equal or even superior to prostate specific antigen (PSA) as a diagnostic marker. This is the conclusion of Dr. Alexander Hermani and colleagues at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ).

And at the University of Sheffield, UK Dr. Ishtiaq Rehman and team say a urine test for Calgranulin B (S100A9), which is a member of the calcium binding protein family, looks promising as a way to detect prostate cancer and prostate cancer recurrence.

Compared to the PSA test, which indicates elevated prostate specific antigen levels also in the case of benign (non-cancerous) conditions, S100A9 is better suited to discriminate cancer from benign prostatic hyperplasia, Dr. Hermani says on the basis of his study of 75 prostate cancer patients.

Members of the S100 protein family, including S100A9, are associated with specific tumors such as liver, lung, and breast cancers. In the blood of ovarian cancer patients, elevated levels of S100A8 and S100A9 have been detected. Scientists also believe that S100 proteins serve as ligands that can bind to the RAGE receptor. The receptor-ligand complex appears to trigger a cellular signaling cascade that ultimately influences a cell's dividing and traveling behavior.

These data and findings served as a starting basis for the work of Alexander Hermani and Professor Dr. Doris Mayer, head of the DKFZ research group "Hormones and Signal Transduction." They investigated tissue samples from human prostate tumors in various stages. In collaboration with colleagues and partners at the University Hospitals in Mannheim, they found that the two members of the S100 protein family and their potential receptor are produced in precursors of cancer and, in increasing amounts, in advanced tumors of the prostate. In contrast, they detected none or only low levels of these proteins in benign tissue.

They also investigated whether S100A9 is found in the blood. If so, it would qualify as a characteristic marker of prostate cancer. They found, indeed, that compared to healthy individuals or patients with benign prostate conditions, S100A9 levels in the blood of cancer patients are significantly elevated.

Particularly relevant is the higher specificity of S100A9 detection. While the PSA test does not facilitate clear discrimination between benign and malignant prostate conditions, S100A9 makes it easier to differentiate between these two conditions.

The Heidelberg results may also prove valuable for prostate cancer prevention and novel treatment concepts. Thus, the complex of S100 ligand and its receptor provides a potential target for special treatment strategies, the investigators claim.

Dr. Ishtiaq Rehman in Sheffield says a recent study aimed at identifying novel biomarkers for the early detection of prostate cancer in voided urine, identified Calgranulin B (S100A9), as "a promising candidate, since it was detected in the urine of men with cancer but was absent in men without cancer."

"Our ability to treat prostate cancer rests on a better understanding of the molecular mechanisms underlying tumour development and progression," Dr. Rehman says. "We are applying Proteomic techniques to identify novel dysregulated proteins involved in the development and progression of human prostate cancer."

Dr. Rehman's website gives a useful summary of aim of studies involving other members of the calcium binding protein family which, studies have shown, are dysregulated (or messed up) in prostate cancer. These include S100A2, S100A4, S100A6, S100A11, any or all of which are "likely to be involved in tumour development and progression," he says.

"The mechanism underlying the loss of expression of S100A6," Rehman says, "was shown for the first time to involve promoter hypermethylation. Ongoing projects are aimed at

• Investigating the involvement of other members of the calcium binding protein family in prostate cancer progression, as well as other cancers
• Identifying genes and signalling pathways involved in the metastatic progression of prostate cancer
• Investigating the role of S100A11 in prostate cancer progression (iv) Establishing whether gene expression differs in cancer cells found in bone and in the primary tumour.