A gene blamed for many human cancers may someday guide surgeons who want to make sure they have rid their patients of disease and haven't left any malignant cells behind, doctors from the Johns Hopkins School of Medicine said today.
Until now, the fast-growing science of cancer genetics has provided scientists with hope of identifying people who are predisposed to deadly cancers -- such as those of the breast and colon -- so doctors and patients can watch for the first suspicious signs.
An article published in today's New England Journal of Medicine presents an additional possibility: that genetic "probes" can do a better job than microscopes of finding residual cancer cells in tissues bordering visible tumors.
The test holds the potential of reducing the frequency of recurrences after cancer operations.
"The biggest problem now is the fact that there are cells that can't be taken out because they can't be seen," said Dr. David Sidransky, a specialist in head and neck cancers who directed the study. "In many cases, if the surgeon could go back and take one more small piece, he could cure the patient."
The Hopkins study involved 69 patients who had head and neck cancers -- a category that includes cancers of the lip, mouth, tongue, jaw and tonsils. In all cases, surgeons removed the visible tumor and a thin rim of tissue that appeared to be healthy.
Pathologists ordinarily inspect the extra tissue under a microscope to make sure that it doesn't contain any cancer cells. Residual cancer cells are often signs that surgeons should remove additional tissue to prevent cancer from spreading. In the study, doctors subjected the extra tissue to a genetic test as well.
When tissues were examined under a microscope, doctors identified 25 patients who appeared to have no cancer cells in the tissue outside their visible tumors. But when doctors used a genetic probe to look for a defective gene known as p53, they found the mutation lurking in the cells of 13 of the patients.
To the doctors, this meant that the microscopes weren't sensitive enough to detect cancers that were brewing on the molecular level. However, they weren't allowed to intervene because the genetic technique is considered experimental. In the two years that followed surgery, five of the patients had recurrences. Four of them died.
"This is almost always the case in head and neck cancers," Dr. Sidransky said. "If you recur, you die. Your first shot is your best shot."
nTC When healthy, the p53 gene puts the brakes on cancer before it accelerates out of control, spreading to nearby cells and distant tissues. A defective gene allows cancer to grow unfettered. The mutation is present in half of all cancers of the head and neck, as well as many breast cancers. The Hopkins team will soon test the technique on 200 patients to confirm the results. If the test proves accurate, Dr. Sidransky said, it could be ready for routine application at major medical centers in a few years.
A major limitation is that half of all head and neck cancers involve different mutations. Dr. Sidransky said he is trying to refine another test that could detect genetic features that are common to all mutations.
Besides signaling the need for more surgery, genetic tests could also rule out unnecessary cutting. This is especially important in the delicate region of the head and neck, where uncertainties about the precise extent of a patient's cancer often force the removal of an extra "margin of safety" at great cost to the patient's quality of life.
"Every little space may make a huge difference in the patient's ability to taste, swallow or speak," Dr. Sidransky said.
Dr. Sheila Taube, chief of the cancer diagnosis branch of the National Cancer Institute, said the study is encouraging. "I think this is probably one of the most appropriate uses of these new molecular techniques," she said. "It allows you to look beyond what the eye can see."
But she said the study does not answer an important question: whether improving surgical accuracy actually improves a patient's chances of survival.