Tissue of Origin Test
FAQ

Frequently asked questions


What is the Pathwork® Diagnostics Tissue of Origin Testing Service?
The Pathwork Tissue of Origin Testing Service aids in the diagnosis of metastatic and difficult to diagnose cancers by comparing the molecular profile in a patient’s tumor tissue sample with the profiles of 17 known tumor types and 69 morphologic subtypes. This service, which covers more than 95% of all solid tumors, includes the original Tissue of Origin Test. The service also includes the Tissue of Origin Endometrial Test and the Tissue of Origin Head & Neck Test, used by the Pathwork Diagnostics pathologist in combination with the original Tissue of Origin test to provide the most accurate result.

What is the Pathwork Tissue of Origin Test?
The Pathwork Tissue of Origin Test is an innovation in molecular diagnostics—a gene expression based test that uses a tumor’s own genomic information to help identify 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 2000 genes, in a tumor and compares it to expression patterns of a panel of 15 known tumor types, representing 58 morphologies and covering 90 percent 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. The FDA-cleared Tissue of Origin Test is available through the CLIA-certified, CAP-accredited Pathwork Diagnostics Laboratory and uses formalin-fixed, paraffin-embedded (FFPE) specimens. An in vitro diagnostic (IVD) kit will be available from Pathwork in the future.

What is Pathwork Diagnostics?
Pathwork Diagnostics, Inc., is a privately held company based in Redwood City, California, that develops and delivers innovative, high-value molecular diagnostics for oncology. The company provides the Tissue of Origin Test through its CLIA-certified, CAP-accredited laboratory.

How does a Genomic Test differ from a Genetic Test?
Genetics tests look at variations in a single gene that may result in an inheritable disease.  Genomic tests look at many genes (sometimes the entire human genome) and assess the activities of the genes themselves as they relate to particular diseases.The Tissue of Origin Test is a genomic test.

What is the Pathwork Diagnostics Laboratory?
The Pathwork Diagnostics Laboratory is a CLIA-certified, CAP-accredited laboratory located in Redwood City, California. For the Pathwork Tissue of Origin Test, physicians can provide FFPE specimens to the laboratory for processing and analysis. A Pathwork staff pathologist interprets the results and provides a comprehensive report to the physician. 

How significant a problem are metastatic tumors that are undifferentiated or poorly differentiated?
The American Cancer Society estimates that there are 1.5 million new cancer diagnoses annually in the United States. Of these new cases, up to 10 percent are tumor types not readily classifiable in the course of the initial diagnostic workup.1 These tumors are among the most frustrating for physicians, and place a disproportionate burden on patients, healthcare professionals, and the healthcare system.

Why is it important to know a tumor’s origin?
Knowing the primary tissue type with greater certainty helps physicians choose the most appropriate treatment regimens. Patients may benefit from:

  • Reduced need for repeated testing, examinations, imaging procedures, or biopsy procedures.
  • Opportunity to enter appropriate clinical trials.
  • Important information in assessing one’s familial risks for cancer.

What are the current methods used to classify a metastatic tumor that is undifferentiated or poorly differentiated?
Diagnostic workups for these challenging tumors typically include extensive immunohistochemistry (IHC) and various imaging studies, such as x-rays, CT scans, and PET scans. Obtaining results for these can often take weeks as clinicians rely on an iterative approach. IHC does not cover all tumor types and requires human review that can be subject to errors. One study showed that IHC was only 65 percent accurate at identifying the primary site of metastatic tumors.2

What makes these tumors so difficult to diagnose?
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.

A recent study of 111 cases derived from 66 academic and community practices showed that after receiving the Tissue of Origin Test results for patients with difficult-to-diagnose primary cancers, the oncologist’s determination of the primary diagnosis was changed in the majority of patients and cancer-specific management changed for two-thirds of the patients. A majority of the oncologists identified the Tissue of Origin Test results as influencing the decision to make a change in therapy. 4

Has the FDA cleared the Tissue of Origin Test?
The U.S. Food and Drug Administration (FDA) has cleared the Pathwork Tissue of Origin Test for use with formalin-fixed, paraffin-embedded (FFPE) tissues. The Pathwork Tissue of Origin Test is the only test of its kind to receive FDA clearance. FDA clearance will allow Pathwork Diagnostics to manufacture IVD kits to be available in the future.

Is the Tissue of Origin Test covered by Medicare?
Palmetto GBA, the contractor that administers Medicare in California, has issued a positive coverage policy for the Pathwork Tissue of Origin Test. Because all Tissue of Origin test specimens are processed in the Pathwork Diagnostics Laboratory in California, the Palmetto decision enables the test to be covered for Medicare patients across the nation.

What other regulatory or professional organizations have endorsed or recommended the Tissue of Origin Test and the Pathwork Diagnostics Laboratory?
The Florida Society of Clinical Oncologists (FLASCO) and the Medical Oncology Association of Southern California (MOASC) have recommended the use of the Tissue of Origin Test to assist in determining tumor origin.

The Centers for Medicare & Medicaid Services (CMS) has certified the Pathwork Diagnostics Laboratory through its Clinical Laboratory Improvement Amendments (CLIA) program. The Pathwork Diagnostics Laboratory has also been awarded accreditation by the College of American Pathologists (CAP), whose Laboratory Accreditation Program is recognized by the federal government as being equal to or more stringent than the government’s own inspection program. The Laboratory is licensed to provide the testing service in every state.

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 15 tumor types: bladder, breast, colorectal, gastric, hepatocellular, kidney, non-small cell lung, non-Hodgkin’s lymphoma, melanoma, ovarian, pancreatic, prostate, soft tissue 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 accuracy of the diagnosis. 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 percent of solid tumors, including those most likely to metastasize. In addition, based on input from oncologists, these 15 types of cancer were considered the most challenging and, once identified, would have the most clinical value in terms of treatment decisions.

What information is added by the Tissue of Origin Endometrial Test?
The Tissue of Origin Endometrial Test, a laboratory developed test that analyzes 14 different morphologic subtypes using a 316–gene classification model, was developed to aid in resolving diagnostic questions in gynecologic oncology and reports the more likely tissue of origin between endometrial and ovarian cancer.

What diagnostic questions was the Tissue of Origin Endometrial Test Designed to Address?
The Tissue of Origin Endometrial Test was developed to aid in resolving diagnostic questions in gynecologic oncology. Cancers that are either metastatic or involve both the ovary and endometrium can present a diagnostic dilemma. For example, endometrial cancers metastatic to the ovary can often mimic ovarian primaries on gross and microscopic examination.

What information is added by the Tissue of Origin Head & Neck Test?
The Tissue of Origin Head & Neck Test, a laboratory developed test, analyzes two morphologic subtypes, squamous cell carcinoma of the head and neck and squamous cell carcinoma of the lung, and uses a using a 2160–gene classification model to report the more likely tissue of origin from between the two.

What diagnostic questions was the Tissue of Origin Head & Neck Test Designed to Address?
The Pathwork Tissue of Origin Head & Neck Test distinguishes head and neck squamous from lung squamous cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 2160–gene classification model. Patients with head and neck squamous cell carcinoma commonly develop second primary squamous cell carcinomas in the lung. Because the histologic appearance of the head and neck tumor and the lung tumor is similar, the differential diagnosis between metastasis or second primary is often unresolved.

How were the Tissue of Origin Endometrial Test and Head & Neck Test Created?
These laboratory developed tests were created under same rigorous product development requirements as the original Tissue of Origin Test, which gained FDA clearance in 2010.  Pathwork plans to seek FDA clearance for these tests as well.

How are the Tissue of Origin Endometrial Test and Head & Neck Test Used?
When certain differential diagnostic questions occur in the process of identifying tissue of origin, the Pathwork Diagnostics pathologist will use the Tissue of Origin Endometrial Test and the Head & Neck Test in combination with the original Tissue of Origin test to provide the most accurate result.

When should the Pathwork Tissue of Origin Test be ordered?
With metastatic tumors or primary tumors that are undifferentiated or poorly differentiated, the Tissue of Origin Test can fill the information gap with accurate, objective, actionable information. The physician can order the test when:

  • The cancer is found in an unexpected location
  • The cancer is found in multiple locations, indicating metastatic disease
  • The tumor is poorly differentiated or undifferentiated
  • There is an unresolved differential diagnosis of 2 or more cancer types
  • The patient has a history of multiple cancers
  • IHC are inconclusive or conflicting
  • The specimen is small, constraining the diagnostic work up and limiting prognostic studies
  • Clinical history and histology differ on the diagnosis
  • There is an atypical distribution of metastases
  • The diagnosis is questioned when the patient fails to respond to treatment

Physicians who order the Tissue of Origin Test do not need to request the Tissue of Origin Endometrial Test or the Tissue of Origin Head & Neck Test; the pathologists of the Pathwork Diagnostics Laboratory will perform these tests when they are needed in the tissue of origin diagnostic process.

Do private health plans cover the test?
Pathwork is working with insurance companies to secure coverage for the test. Insurance companies are paying for the test on a case by case basis at this time. Pathwork reimbursement counselors will 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 their doctor.

What are the specimen requirements for the test?
Acceptable specimen types include:

  • FFPE Block:
  • Send a block containing at least 1 mm2 of TUMOR tissue by area. Include an H&E stained slide if possible.
  • Unstained Slides (USS):
  • Send unstained slides of at least 5 μm-thickness (10 μm-thickness preferred) that contain no less than 1 mm2 of TUMOR tissue.
    • For tumor areas < 5 mm2 – send at least 8 USS
    • For tumor areas ≥ 5 mm2 – send at least 5 USS

For complete specimen collection and shipping requirements, please visit www.pathworkdx.com.

Can the test be performed on body fluid specimens?
A study published in the peer-reviewed journal Cancer Cytopathology demonstrated the capability of the Tissue of Origin Test to be performed on a variety of body fluid cytology specimens preserved in FFPE. The test successfully yielded results in 89% of the specimens examined and correctly identified the available diagnosis with a 94.1% agreement.5

Whom should I contact to order the test through the Pathwork Diagnostics Laboratory?
Call the Pathwork Diagnostics Laboratory Customer Support toll-free at 1.877.808.0006 or email support@pathworkdx.com.

 

References

1 Pathwork market research data on file. Pathwork Diagnostics: 2008.
2 Dennis JL, Hvidsten TR, Wit EC, et al. Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clin Cancer Res. 2005;11(10):3766-3772.
3 Pillai et al: Microarray-based gene expression assay for identification of primary site using formalin-fixed paraffin-embedded (FFPE) tissue. Poster presented at ASCO-GI, January 2010, Orlando, FL
4 Hornberger et al. Effect of a gene expression-based tissue of origin test's impact on patient management for difficult-to-diagnose primary cancers. Poster presented at the 2011 ASCO Gastrointestinal Cancers Symposium; January 22, 2011; San Francisco, CA.
5 Stancel et al. Identification of tissue of origin in body fluid specimens using a gene expression microarray assay. Cancer Cytopathology. June 29, 2011. doi: 10.1002/cncy.20167.