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Eye cancer tumors likely to spread can be identified by genetictest by 123wert sdfsf
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Eye cancer tumors likely to spread can be identified by genetictest |
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Researchers at Washington University School of Medicine in St.Louis have developed a genetic test that can accurately predictwhether the most common form of eye cancer will spread to other parts of the body, particularly the liver. In 459 patients with ocular melanoma at 12 centers in the United States and Canada, the researchersfound the test could successfully classify tumors more than 97percent of the time. The study will appear in an upcoming issue of the journal Ophthalmology, but is now online. "When the cancer spreads beyond the eye, it's unlikely any therapyis going to be effective," says principal investigator J. WilliamHarbour, MD.
"But it's very possible that we can develop treatmentsto slow the growth of metastatic tumors. The real importance ofthis test is that by identifying the type of tumor a patient has,we can first remove the tumor from the eye with surgery orradiation and then get those individuals at high risk into clinicaltrials that might be able to help them live longer." Harbour believes the test should allow ocular oncologists toquickly evaluate the risks associated with particular tumors and tobegin treatment the moment they can detect any spread of thecancer. Melanoma of the eye is relatively rare, diagnosed in about 2,000 people inthe United States each year. Advances in treatment have allowedsurgeons to preserve patients' vision, but when cancer spreadsbeyond the eye, it often is deadly.
About a decade ago, Harbour, the Paul A. Cibis DistinguishedProfessor of Ophthalmology and Visual Sciences, began using geneexpression profiling to monitor the activity of thousands of genesin and around ocular melanoma tumors. "At the time, we were surprised to see that based on these geneexpression profiles, the tumors clustered into two groups thatcorresponded, almost perfectly, to patients whose cancer spread andthose whose cancer was confined within the eye," says Harbour, whodirects Washington University's Center for Ocular Oncology. "Tumorswith a class 1 gene expression profile, or 'signature,' very rarelyspread, but those with a class 2 profile frequently develop intometastatic cancer." Initially, Harbour's group identified differences in approximately1,000 genes between class 1 and class 2 tumors, but they whittleddown that number, hoping to develop a simple test that could beused easily by ophthalmologists. Eventually, they settled on abouta dozen genes that could be evaluated in tumor samples collectedwith a needle biopsy.
"We went through a number of sophisticated algorithms andvalidations, and we came up with a group of 12 genes," he says. "Wealso included three more genes that don't change whether they arein tumor tissue or healthy tissue. Those genes act as our'controls' in this prognostic test." Testing tumor tissue from his own ocular melanoma patients at theAlvin J. Siteman Cancer Center at Barnes-Jewish Hospital andWashington University in St.
Louis, Harbour found that the geneexpression profile test was very good at identifying the twoclasses of tumors. Then he started recruiting other centers to testthe method, too. "It doesn't make for a good test if it works really well for us,but it doesn't really work for anybody else," Harbour says. Doctors at the other centers collected tumor samples and shippedthem to Harbour's lab. Not knowing anything about which tumorsamples came from which patients, the lab then analyzed the samplesand made predictions about which tumors were likely to spread.Although it can take up to five years before there is any evidencethat cancer has spread beyond the eye, this study went back lessthan two years later and tested predictions against what actuallyhad happened.
Almost 62 percent of those tested (276 patients) had class 1tumors, which were unlikely to spread. About a year and a halfafter the samples were tested, only three of those tumors hadmetastasized. Meanwhile, 38 percent of those tested (170 patients)had class 2 tumors, indicating that spread of the cancer was morelikely. In that group, 44 (26 percent) developed metastatic diseaseduring the study period.
Had patients been followed longer, morelikely would have experienced spread of their cancer. Statisticalpredictions estimate that among class 2 patients, about 60 percentwould have metastatic disease within three years, and approximately80 percent in five years. "In this relatively short study period, the test worked as well asin the larger group of patients as it had in our patients," Harboursays. "That was important because it validated not only that ourtest was an accurate predictor of which patients will developmetastasis, but it also proved that the test can be performedsuccessfully in most other clinics.
At the moment, more than 70centers around the world are using a commercially available versionof the same test." In the past, some centers relied on a chromosome test to identifyeye tumors that were likely to spread. That test looked atchromosome 3 because many ocular melanoma tumors have only one copyof that chromosome. But the 15-gene expression profile test is more accurate. It takesa more complete "snapshot" of the entire tumor. Harbour says theresults of the chromosome test can change, depending on which partof a tumor gets sampled.
"I compare it to how our brains recognize faces," he says. "Wedon't just focus on somebody's nose. We take in all of theinformation from the entire face. This test takes information fromthe entire tumor, so if the 'nose' in the 'picture' is out of focusfor some reason, it still can analyze other things." Another strength of the test, he says, is that it can identifywhich patients will need the closest monitoring.
"Here at Washington University, for example, we monitor patientswith class 2 tumors every three months and can begin treatmentright away if we find evidence that a tumor has spread," he says. On the other hand, the current study found that more than 60percent of patients with ocular melanoma have class 1 tumors. Thosepatients don't need to be followed with the same frequency. "We won't have to use high-intensity surveillance on everyone, onlyon those patients with a class 2 molecular signature, becausethey're the ones at risk for metastatic cancer," Harbour says.
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