What is the CGI Tissue of Origin Test?
The CGI 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 measures the expression pattern, comprising more than 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 CGI Laboratory and uses formalin-fixed, paraffin-embedded (FFPE) specimens.
What is the CGI Tissue of Origin Testing Service?
The CGI 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 CGI pathologist in combination with the original Tissue of Origin test to provide the most accurate result.
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. A 2013 study showed that the Tissue of Origin Test is more accurate than IHC.
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 CGI Tissue of Origin Test?
The CGI 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.3
In a reproducibility analysis, the Tissue of Origin Test demonstrated an average 89% overall concordance across three laboratories in a cross-laboratory comparison study of 149 metastatic and poorly differentiated and undifferentiated tissue specimens.3
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 CGI Tissue of Origin Test for use with formalin-fixed, paraffin-embedded (FFPE) tissues. The CGI Tissue of Origin Test is the only test of its kind to receive FDA clearance.
The Centers for Medicare & Medicaid Services (CMS) has certified the CGI Laboratory through its Clinical Laboratory Improvement Amendments (CLIA) program. The CGI 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 CGI Tissue of Origin Test report include?
For each tumor specimen, the CGI 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 CGI Tissue of Origin Test Clinical Report is interpreted and signed by a CGI 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 375–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 2600–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 Tissue of Origin Head & Neck Test distinguishes head and neck squamous from lung squamous cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 2600–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 2009.
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 CGI 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.
How do physicians use the results of the Tissue of Origin Test?
The test’s highly accurate and reproducible results are evaluated by the physician in addition to the patient’s clinical history and complementary diagnostics, such as immunohistochemistry and imaging, to make a tissue of origin diagnosis.
When should the CGI 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 tumor is poorly differentiated or undifferentiated.
- There is an unresolved differential diagnosis of 2 or more cancer types
- The specimen is small, constraining the diagnostic work up and limiting prognostic studies
- The patient has a history of multiple cancers
- IHC are inconclusive or conflicting after the first round
- Clinical history and histology differ on the diagnosis
- There is atypical distribution of metastases
- Oncology and Pathology differ on the diagnosis
- 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 CGI Laboratory will perform these tests when they are needed in the tissue of origin diagnostic process.
Do private health plans cover the test?
CGI 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. CGI’s 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.
o For tumor areas < 5 mm2 – send at least 8 USS
o For tumor areas ≥ 5 mm2 – send at least 5 USS
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