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Area Around Breast Tumor May Predict Cancer's Spread
Date:12/19/2007

Mutations in tumor-suppressing gene could point to lymph node involvement, study suggests

WEDNESDAY, Dec. 19 (HealthDay News) -- Supposedly "innocent" cells in the area surrounding cancerous tumors in the breast are definitely not always innocent and can predict whether or not the cancer spreads to the lymph nodes, new research suggests.

The finding of alterations in the tumor-suppressing p53 gene in the stroma -- the region surrounding the tumor -- have future implications, the researchers said.

"The stroma looks innocent under the microscope, but there's an evil seed in innocent soil," said study senior author Dr. Charis Eng, chair of the Cleveland Clinic Genomic Medicine Institute in Ohio.

"This could be a new type of [cancer] biomarker, p53 in the stroma," she added.

In addition, the findings may one day eliminate the need to remove and dissect the lymph nodes which, as Eng points out, is a "nuisance" to patients.

Even further down the line, the stroma might provide a new target for drug therapies.

"It's a significant study," said Steve A. Maxwell, an associate professor of molecular and cellular medicine at Texas A&M Health Science Center College of Medicine, in College Station. "Treatments targeting p53 in the stroma might lead to suppression of spread [of the cancer] or to prevention of recurrence. I don't see it as a cure, but it could contain future spread."

Further research is needed before any of these scenarios become reality, the researchers said.

The findings are published in the Dec. 20 issue of the New England Journal of Medicine.

"Communication" between a tumor and the stroma is increasingly a subject of research.

So is p53, a much-studied oncogene. P53 is involved in repairing DNA damage and other functions which prevent cells from turning malignant. This gene is mutated in 20 percent to 50 percent of breast cancers.

In 1999, Eng's group looked at seemingly harmless stromal cells and found that they had cancer-related mutations in the p53 gene.

For this study, the group looked at whether genetic alterations in the stroma had any impact on clinical outcomes, and if they could predict the spread of the cancer.

To this end, they analyzed tissue samples from 218 breast cancer patients: 43 with hereditary breast cancer and 175 with sporadic breast cancer.

A technique called laser-capture microdissection was used to take individual breast cancer cells and surrounding stromal cells.

Mutations in p53, in the stroma but not in the cancer, increased the chances that the cancer would spread to the lymph nodes, indicating a worse outcome for these patients.

But even when the p53 alteration was not present, changes in five other markers resulted in the same outcome.

In other words, changes in the microenvironment surrounding a tumor can impact how the cancer spreads, the research suggests.

A second study in the same issue of the journal found that mutations in the same p53 gene were associated with shorter survival after surgery in patients with squamous-cell carcinoma of the head and neck.

This type of cancer is one of the most common cancers in the world; more than 45,000 new cases are expected to be diagnosed in the United States in 2007.

P53 mutations in general and a specific p53 mutation were associated with poorer survival, reported a team led by Dr. Wayne Koch, of Johns Hopkins University, Baltimore.

More information

There's more on the p53 gene at the U.S. National Library of Medicine.



SOURCES: Charis Eng, M.D., Ph.D., chair, Cleveland Clinic Genomic Medicine Institute, Ohio; Steve A. Maxwell, Ph.D., associate professor, molecular and cellular medicine, Texas A&M Health Science Center College of Medicine, College Station; Dec. 20, 2007, New England Journal of Medicine


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