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GE, Clarient Move MultiOmyx Platform into Clinic with Launch of Hodgkin Diagnostic

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With the launch this month of its Hodgkin Lymphoma Profile diagnostic, GE Healthcare has moved its MultiOmyx protein detection system into the clinical arena.

Offered through the company's Clarient Diagnostic Services, the HL Profile test assesses the levels of nine proteins linked to Hodgkin, and is intended as an aid to diagnose the disease where conventional methods are either impractical or insufficient.

According to Lawrence Weiss, medical director at Clarient, the company has used the test for assessing five patient samples in the last week, in several cases providing a definitive diagnosis where conventional immunohistochemistry and flow cytometry techniques had failed to do so.

Introduced by the company in February and launched as a research device in May, the MultiOmyx platform uses antibodies conjugated to fluorescent dyes to stain proteins of interest in batches of two to four at a time. Researchers then image the stained tissue and deactivate the fluorescent dyes via a proprietary process. They can then stain the tissue with the next round of antibodies, multiplexing in an iterative fashion.

In a February interview, Michael Gerdes, a GE Global Research biologist and leader of the platform development effort, told ProteoMonitor that company researchers had measured as many as 65 proteins in a single sample and could potentially multiplex significantly more (PM 2/15/2013).

The company has antibodies to more than 175 markers ready for use with the platform. In experiments to test for background resulting from multiple staining cycles, the researchers have found no added background after as many as 100 cycles.

In addition to its multiplexing abilities, the platform also allows researchers to obtain spatial information on the detected markers, offering subcellular resolution.

These features, Weiss told ProteoMonitor, made the platform a natural fit for diagnosis of Hodgkin lymphoma, a disease where clinicians are often working to identify multiple markers within very small populations of cells.

Typically, the cells responsible for Hodgkin disease "represent only about one percent of the population in a lymph node. So it's sort of a rare event," he said. "And what you are doing with conventional immunohistochemical studies is doing a bunch of immunostains, each on a different slide, and then trying to think, are they on the same population or are they not on the same population?"

"Sometimes [using conventional methods] it's pretty clear when there are a lot of atypical cells," Weiss said. "But a lot of the time it's guesswork."

He provided examples from several of the five Hodgkin lymphoma cases run on the platform in the last week. In two cases, the needle biopsies provided were so small as to allow for conventional immunostaining of only "two or three out of a minimum of six [proteins] that we wanted," he said. "So we went to MultiOmyx and one [case] is still pending, and the other we were able to give a definitive diagnosis."

In another case, conventional immunohistochemistry was unable to exclude Hodgkin disease due to the presence of cells positive for the Hodgkin protein marker CD30 and for the marker CD15. The key question, Weiss noted, was whether these markers were expressed on the same cells – indicating Hodgkin – or on different cells – ruling out the disease.

With conventional pathology, this can be difficult to determine, he said. "We have some CD30 positive cells on one slide. We look at another slide and we have some CD15 positive cells. But we don't really know whether they are the same cells or not."

With the MultiOmyx test, on the other hand, Weiss was able to determine "clearly that the CD30 positive cells were CD15 negative," meaning that the patient did not have Hodgkin disease, he said.

Due to its high cost – which Clarient declined to disclose – relative to conventional methods, the platform is currently reserved for particularly tough calls, Weiss said, estimating that it would be needed in around a quarter or fewer of Hodgkin disease cases. However, he said, "ultimately, when the price comes down, I would love to have MultiOmyx replace immunohistochemistry for lymph node evaluation."

With a turnaround time of four to five days per sample, the platform is also slower than conventional immunohistochemistry. However, Weiss noted, "if it is going to provide a better diagnosis, [the extra time] is easily worth it."

He suggested peripheral T cell lymphoma as another disease for which the platform would be well suited, noting that roughly 75 percent of such cases need expert interpretation.

"What we're looking for [in peripheral T cell lymphoma] is aberrant loss of T cell antigens on a T cell population, and that can be very difficult to determine when you are just looking at large populations of cells by immunohistochemistry," he said. "Loss has to be seen in pretty much greater than 50 percent of the population before we can have any degree of confidence that we are seeing it. But with MultiOmyx we can just look at individual cells and see if there is [antigen] loss."

Eventually, Weiss said, he would hope to add B cell lymphomas, offering "a complete panel for lymph node work-up."

Less than a month old, the MultiOmyx clinical offerings are still in their infancy, and currently, Weiss said, he is the only pathologist approved on the platform for clinical work. Clarient sells the HL Profile as a laboratory-developed test, but longer term, the company is considering developing the technology as a device for selling into clinical pathology settings.

In addition to clinical work, the platform is also intended as a research tool. Upon introducing the system in February, GE announced a collaboration with Vanderbilt University to continue development of the platform as part of work on colon cancer led by Vanderbilt researcher Robert Coffey. That work is supported by a five-year, $3.75 million grant from the National Institutes of Health.

This month, GE researchers published a paper in the Proceedings of the National Academy of Sciences detailing use of the platform to measure 61 proteins in formalin-fixed paraffin-embedded tumor samples from 747 colorectal cancer patients. Among the findings enabled by the technique's multiplexing capabilities and sub-cellular level resolution was that high-level phosphorylation of the mTORC1 targets 4E-BP1 and RPS6 rarely occurs in the same cell, suggesting, the authors wrote, that "mTORC1 uses discrete mechanisms or binding partners to interact with its substrates."

The company has also published several posters detailing research done on the platform, including a study done with University of Toronto researchers on co-localization of Her2/Neu, ER, PR, Ki67, and cytokeratin in triple-positive breast cancer and studies with State University of New York, Albany researchers on signaling and cell population dynamics in developing salivary glands.

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