Frequently asked questions

What is the Pathwork Tissue of Origin Test?

The Pathwork Tissue of Origin Test, cleared by the FDA in 2010, is an innovation in molecular diagnostics—a gene expression-based test that uses a tumor's own genomic information to indicate its origin. The test provides objective data previously unavailable to physicians for tissue of origin identification. The Tissue of Origin Test, developed by Pathwork Diagnostics, measures the expression pattern, comprising more than 2,000 genes, in a tumor to compare it to expression patterns of a panel of 15 tumor types, representing 58 morphologies and covering 90% of all solid tumors. It produces a report with an objective score for each potential tissue. The test uses a proprietary Pathchip^® microarray and runs on the proven Affymetrix GeneChip^® System.

What is the Pathwork Diagnostics Laboratory?

The Pathwork Diagnostics laboratory is located in Redwood City, California. For the Pathwork Tissue of Origin Test, physicians can provide FFPE tissue specimens to the laboratory for processing and analysis. A Pathwork staff pathologist interprets the results and provides a comprehensive report to the physician. Through the Pathwork Reimbursement Assistance Program (RAP), the company provides assistance to patients whose insurance companies may not yet cover the test.

How significant a problem are tumors that cannot be readily classified?

The American Cancer Society estimates that there are 1.4 million new cancer diagnoses annually in the United States. Of these new cases, up to 10% are tumor types not readily classifiable in the course of the initial diagnostic workup.¹ These tumors, which may be metastatic, undifferentiated, or poorly differentiated, are among the most frustrating for physicians, and place a disproportionate burden on patients, health care professionals, and the health care system.

Why is it important to know a tumor's origin?

Knowing the primary tissue type with greater certainty helps physicians prescribe prompt treatment with the most appropriate regimens. This means patients may benefit from:

• Effective targeted therapies
• Less exposure to broad-spectrum therapies that may be more toxic and ineffective
• Less need for repeated testing, examinations, imaging procedures, or biopsy procedures
• Opportunity to enter appropriate clinical trials
• Important information in assessing one's familial risk for cancer

Why is knowing a tumor's origin important for patients receiving targeted cancer therapies?

Targeted therapies can be effective even with metastatic tumors and are generally tumor-specific (e.g., Herceptin^® for breast cancer), but this requires identification of the primary tumor site/tissue of origin. Targeting therapy to specific tumor types may allow patients to avoid the toxicity of broad-spectrum, and in some cases ineffective, chemotherapy.

What are the current methods used to identify these challenging tumors?

Diagnostic workups for these tumors typically include extensive immunohistochemistry (IHC) and various imaging studies, such as x-rays and computed tomography. Obtaining results for these can often take weeks as clinicians rely on a trial-and-error and necessarily iterative approach.The Pathwork test, which takes 7 to 11 days to provide objective data for tumor classification, can be a valuable adjunct to existing methods.²

Why is the origin of some tumors so difficult to identify?

A tumor's site of origin may be elusive because the original tumor may be small, avoiding detection by imaging and other techniques. Additionally, cells of the tumor in question may have changed appearance and thus may no longer resemble tumors from the originating site (i.e. they have become poorly differentiated or undifferentiated).

What is the clinical performance of the Pathwork Tissue of Origin Test?

The Pathwork Tissue of Origin Test is supported by extensive analytical and clinical validation data.

• In 462 FFPE specimens, the test demonstrated 89% positive percent agreement (akin to sensitivity) with available diagnoses, and greater than 99% negative percent agreement (akin to specificity) in specimens that had previously been identified with existing methods as being among the 15 tumor types on the panel.

Is the Pathwork Tissue of Origin Test currently available?

Yes. Physicians may order the Pathwork Tissue of Origin Test as a service through the Pathwork Diagnostics laboratory. FFPE specimens may be provided to the Pathwork Diagnostics laboratory for processing and analysis. A Pathwork staff pathologist interprets the results and provides a comprehensive report to the physician within 7 to 11 days.

What does the Pathwork Tissue of Origin Test report include?

For each tumor specimen, the Pathwork Tissue of Origin Test Report provides an objective score for each of the following tumor types: bladder, breast, colorectal, gastric, hepatocellular, kidney, non-small cell lung, non-Hodgkin's lymphoma, melanoma, ovarian, pancreatic, prostate, sarcoma, testicular germ cell and thyroid. The test provides an accurate, objective result with the ability to rule in or rule out tissues to increase the certainty of the diagnosis. When ordered through the Pathwork Diagnostics laboratory, the Pathwork Tissue of Origin Test clinical report is interpreted and signed by a Pathwork staff pathologist.

Why were these 15 cancers chosen?

These 15 tumor types represent 58 morphologies overall and cover approximately 90% of solid tumors, including those most likely to metastasize. In addition, based on input from oncologists, these 15 types of cancer were considered most likely to present as uncertain and, once identified, would have the most clinical value in terms of treatment decisions.

When should the Pathwork Tissue of Origin Test be ordered?

When the tumor is challenging, as is found in metastatic, poorly differentiated or undifferentiated  cancer, the Tissue of Origin Test can help fill the information gap with accurate, objective information. The physician can order the test as a diagnostic aid when:

• The cancer is found in an unexpected location.
• The cancer is found in multiple locations, indicating metastatic disease.
• The tumor cells are poorly differentiated or undifferentiated, making them difficult to interpret.³

Are there any limitations to the use of the IVD Tissue of Origin Test?

Yes, the FDA cleared this product with several limitations. For example, it cannot be used to determine the origin of specimens from patients diagnosed with cancer of unknown primary (CUP). And, specimens from tumors with an origin that is not one of the 15 tissue types in the database will give erroneous test readings. Other limitations to the cleared test are more fully described in the limitations section of the product's Indicated Use statement.

Do health plans cover the test?

Some insurance companies do not yet cover the test automatically. However, Pathwork is working with insurance companies to secure coverage for the test. More than likely, insurance companies will initially begin to pay for the test on a case-by-case basis. In the interim, Pathwork counselors can provide assistance in order to ensure that people who cannot afford to pay for the test will not be denied access if it is recommended by a doctor.

What are the specimen requirements for the test?

Pathwork Diagnostics prefers a block of FFPE tissue containing at least 1 mm² of TUMOR tissue by area.  Include an H&E slide if possible.

If an FFPE block is not available, send unstained slides (USS) of at least 5 um-thickness (10 um-thickness preferred) that contain no less than 1 mm² of TUMOR tissue.

• For tumor areas less than 5 mm² -- send at least 8 USS
• For tumor areas greater than or equal to 5 mm² -- send at least 5 USS

Acceptable specimen types:

• An FFPE block of solid tissue
• FFPE cell buttons from fine needle aspirates (FNA), including bone marrow aspirates
• FFPE cell buttons from malignant effusions
• FFPE core needle biopsies
• Unstained slides from any of the above

Unacceptable specimen types:

• Tissue that has been decalcified
• Any unfixed tissues or fluids
• Wet or frozen tissue, or tissue that has been previously frozen
• Tissue pre-embedded in agar
• Blood or urine

For all specimen types, please ensure that:

• Tissue does not sit on bench for more than 1 hour before fixation
• Tissue is fixed in phosphate buffered formalin for between 6 and 24 hours 

For complete specimen collection and shipping requirements, please visit the Order Test page.

Why did Pathwork choose the microarray platform for this test?

In comparison to other technologies, microarrays enable thousands of genes to be evaluated simultaneously. Using more genes provides better results when analyzing complex and rapidly changing diseases such as cancer and enables better standardization, which yields a more robust test with better reproducibility.

Whom should I contact to order the test through Pathwork Diagnostics Laboratory?

Call the Pathwork Diagnostics laboratory Customer Support toll-free at 1.877.808.0006 or email support@pathworkdx.com.

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