Apr. 18, 2002
     Prostate Cancer

 

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New molecular marker for prostate cancer

BALTIMORE -- Apr. 18, 2000 (Cancer Digest)-- Researchers have found a gene that may be linked to an association between prostate cancer and a diet high in red meat and dairy products.

While previous research has found a strong correlation between red meat consumption and prostate cancer, there has been no biological mechanism identified that could explain the association.

Now a research team led by Dr. William Isaacs of Johns Hopkins' Kimmel Cancer Center has identified a gene called AMACR (xmethylacyl-CoA racemase) that produces nine times as much of its protein in prostate cancer cells than it does in normal tissue. Their findings are reported in the April 15, 2002, issue of Cancer Research.

"This gene appears to play an important role in breakdown of branched-chain fatty acid molecules such as those found in dairy products and beef," Isaacs said in a prepared statement.

The Hopkins scientists caution that the link, if any, between increased production of the AMACR enzyme and eating beef and dairy foods is unclear and remains the focus of ongoing research. Nevertheless, lead author Dr. June Luo says the finding offers possibilities for early detection and prevention of prostate cancer should the link be confirmed.

"Since AMACR enzymatic activity is not found in most normal tissues, it could be an excellent candidate for the development of molecular probes for non-invasive detection of prostate cancer and as a potential drug target," says Luo, a postdoctoral fellow at Johns Hopkins.

In the current study, Hopkins researchers used a comprehensive "gene chip" approach to simultaneously analyze the expression of more than 6,500 genes and found that the enzyme made by the AMACR gene was highly produced in prostate cancers.

They confirmed this by examining 168 prostate cancer tumors using a tissue microarray that rapidly evaluates gene expression. Using automated computer technology, researchers are able to identify which genes are active and which are inactive within a tissue sample. By comparing these patterns of "activity" in normal and cancerous tissue samples, they can identify differences that may play a role in the development of disease.

What they found was that more than 95 percent of the prostate tumors analyzed showed over production of the AMACR gene, making it one of the most consistent biological markers known for prostate cancer. Similar overexpression patterns were found in precancerous lesions, called high-grade prostatic intraepithelial neoplasia.

One possible application of the finding would be to make needle biopsies more accurate. A prostate needle biopsy is an uncomfortable procedure that requires repeated needles to be placed through the rectum into the prostate to retrieve prostate cells for examination under the microscope. According to Dr. De Marzo, assistant professor of pathology and a co-author of the study, using AMACR as a marker could reduce the need for multiple biopsies to confirm a diagnosis of prostate cancer.

"As many as 15 percent of needle biopsies are inconclusive and must be repeated," says De Marzo. "Markers that can enhance diagnostic accuracy the first time are urgently needed."

The Hopkins group currently is studying the effectiveness of using AMACR in combination with a more commonly prostate cancer-associated gene, p63, to evaluate prostate needle biopsies.

The Peter J. Sharpe Foundation, the Charlotte Geyer Foundation and the National Cancer Institute funded this research.


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