A test developed by Pathwork Diagnostics (Sunnyvale, California) that can help healthcare professionals determine what specific type of cancer cells are present in a malignant tumor has been cleared by the FDA.

The Pathwork Tissue of Origin Test uses a microarray to measure the expression pattern, comprising more than 1,500 genes, in the uncertain tumor and compares it to expression patterns of a panel of 15 known tumor types, representing 60 morphologies overall to help determine the tumor's origin.

"It took three years to develop the test," David Craford, VP of Commericial Operations for Pathwork told Medical Device Daily. "This test represents a real milestone for expression-based molecular diagnostics. The feedback we've gotten is positive, and oncologists have said that they were happy [this helps] get them to a stronger diagnosis."

In the in vitro diagnostics clinical validation study submitted to the FDA, the test demonstrated 89% positive agreement (akin to sensitivity) with available diagnoses and 99% negative agreement (akin to specificity).

The study consisted of the analysis of 545 metastatic, poorly differentiated and undifferentiated tumors that had been identified as one of the 15 tumor types on the panel using existing methods. The test demonstrated an average 94% overall concordance across four laboratories in a cross-laboratory comparison study of 60 metastatic, poorly differentiated and undifferentiated tissue specimens.

Microarray technology can simultaneously measure gene expression levels of large numbers of genes. Small DNA fragments are placed or arrayed on a slide and then RNA, which has been extracted from the tumor tissue and labeled with a fluorescent marker, is spread over this "microarray."

Since RNA binds to its complementary DNA strand, the amount of binding indicates how active the gene being evaluated is. This can be determined by putting the array under a scanning microscope and measuring the intensity of the fluorescent light at each point on the array.

"The test is administered through a tissue biopsy," Craford said. "After it is completed you get this report that gives the interpreting pathologist a score of the 15 common tumor type tissues."

Pathwork's software converts the scanned image data to gene expression measurements. The gene expression patterns then are compared with known gene expression patterns in the database that correspond to different tumor types.

"Knowing the primary tumor site with greater certainty enables more appropriate cancer treatment. The growing trend in cancer care is the use of therapies that target specific tissues and their genomic components, rather than relying on a one-size-fits-all treatment approach," said Deborah Neff, President/CEO of Pathwork. "We believe the Pathwork Tissue of Origin Test will help provide more certainty in tumor diagnosis, which will enable more patients to realize the benefits of this new era in genomics-based diagnostics."

The FDA-cleared test will be available as an in vitro diagnostic (IVD) kit, meaning that clinical laboratories can run the test themselves. The test is currently available as a service through Pathwork's CLIA-certified laboratory.

The test also uses PathChip; a gene expression array customed designed for the company by Affymetrix (Santa Clara, Florida). PathChip is the first custom Affymetrix gene expression array to be cleared for diagnostic use.

"Together Affymetrix and Pathwork have developed and now bring to market a very powerful tool to potentially improve cancer diagnostics and subsequent treatment planning and outcome," said Kevin King, president of Affymetrix. "The Pathwork Tissue of Origin Test is supported by extensive analytical and clinical validation data. This not only expands the menu on our diagnostic platform, but opens the door for other gene expression-based diagnostic tests that are currently being developed by Affymetrix and our PbA partners on the GCSDx platform."

FDA said that the Pathwork Tissue of Origin test is the second in vitro diagnostic multivariate index assay (IVDMIA) device that it has cleared. The fist such test was the MammaPrint, developed by Agendia (Amsterdam, the Netherlands). A genetic test cleared early last year, the MammaPrint is used to determine the likelihood of breast cancer returning within five to 10 years after a women's initial cancer (MDD, Feb 7, 2007).

In July 2007, the FDA issued a draft guidance document to address premarket pathways and postmarket requirements for IVDMIAs. IVDMIA tests combine the values of multiple variables to yield a single, patient-specific result.

"The clearance of the Pathwork test is another step in the continued integration of molecular-based medicine into standard practice," said Daniel Schultz, MD, director of the FDA's Center for Devices and Radiological Health. "In the past, scientists have classified different types of cancers based on the organs in which the tumors develop. With the help of microarray technology, they will be able to classify these types of cancers in a standardized non-reader dependent manner based on the patterns of gene activity in the tumor cells."

Pathwork was founded in June of 2006 through an $11 million financing. To date the company said it has received no other financings.