Tissue of Origin® 

The Tissue of Origin test, formally a Pathwork test, is a microarray-based gene expression test that aids in identifying challenging tumors, including metastatic, poorly differentiated, and undifferentiated cancers.  TOO is the ONLY FDA-cleared test of its type and is a Medicare-reimbursed test.

Tissue of Origin® Overview

  • The Tissue of Origin reports the most likely tissue of origin from 15 of the most common tumor types (breast, non-small cell lung, pancreas, gastric, colorectal, liver, bladder, kidney, thyroid, non-Hodgkin lymphoma, melanoma, ovarian, sarcoma, testicular germ cell, and prostate), representing 58 morphologies.
  • 2000 genes, covering 15 tumors types and 90% of all solid tumors¹
  • Extensive analytical and clinical validation.
  • Statistically significant improvement in accuracy over other methods, including IHC²
  • Leads to a change in treatment 65% of the time.

TOO

  1. Validation and Reproducibility of a Microarray-based Gene Expression Test for Identifying the Primary Site of Tumors in Formalin-Fixed Paraffin-Embedded SpecimensR Pillai, R Deeter, CT Rigl, JS Nystrom, M Halks Miller, L Buturovic, WD Henner. J Molec Diag 13 2011;13:48-56
  2. A Multicenter Study Directly Comparing the Diagnostic Accuracy of Gene Expression Profiling and Immunohistochemistry for Primary Site Identification in Metastatic Tumors. CR Handorf, A Kulkarni, JP Grenert, L Weiss, W Rogers, O Kim, F Monzon, M Halks-Miller, G Anderson, M Walker, R Pillai, WD Henner. Am J Surg Pathol 2013;37:1067
  3. Clinical Utility of Gene-Expression Profiling for Tumor-Site Origin in Patients with Metastatic or Poorly Differentiated Cancer: Impact on Diagnosis, Treatment, and Survival. JS Nystrom, J Hornberger, G Varadhachary, R Hornberger, H Gutierrez, WD Henner, S Becker, M Amin, M Walker. Oncotarget 2012 Jun;3(6):620-8 

Clinical Use

When there is clinical uncertainty about a challenging tumor, the Tissue of Origin can help fill the information gap with accurate, objective information. The physician should consider ordering the test as a diagnostic aid 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
  • Immunohistochemistry stains 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

Methodology

CGI processes the specimen, runs the Tissue of Origin and reports the results to the ordering physician. Proprietary analytics are used to interpret the data, and a report is generated that provides clear, objective information on the Similarity Score for each of 15 tumor types, uniquely enabling the healthcare provider to rule in or rule out specific tumor types.

Bladder Kidney Pancreas
Breast Melanoma Prostate
Colorectal Non-Hodgkin’s Lymphoma Sarcoma
Gastric Non-Small Cell Lung Testicular Germ Cell
Hepatocellular Ovarian Thyroid

Each report includes a pathologist’s interpretation of the test results.

How the Test Works

WorkFlow

Clinical Validation

The Tissue of Origin test is supported by extensive analytical and clinical validation data from robust, multi-center clinical studies.* The results of these studies are meaningful because they highlight the test’s accuracy and reproducibility.

  • A large-scale validation study was published in the January 2011 Journal of Molecular Diagnostics. The study comprised 462 metastatic, poorly differentiated, or undifferentiated tumor specimens that had been diagnosed using current methodologies: The test demonstrated 89% positive percent agreement (akin to sensitivity) with available diagnoses and 99% negative percent agreement (akin to specificity) using formalin-fixed, paraffin-embedded (FFPE) tumor specimens, the most common clinical specimen type.1
  • In an independent validation study by the University of California, San Francisco published in Clinica Chimica Acta, 37 FFPE clinical specimens were tested using the Tissue of Origin test. In 95% of the cases, the test results were in agreement with the reference diagnosis.2
  • The Tissue of Origin Endometrial test validation study was published in 2012 and looked at 75 specimens. Using 375 genes, the Test discriminated between Endometrial and Ovarian tissue with 95% accuracy. 14 histologic subtypes were included in the 75 specimens.3
  • In 2013, the validation study for the Tissue of Origin Head & Neck test was published. The test uses 2,600 genes to discriminate between squamous lung and squamous Head & Neck cancer. 76 metastatic or poorly differentiated specimens were analyzed. The test was 83% accurate.4
  • 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.1
  • A study published in the 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

Clinical Utility

  • A 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 oncologists changed the diagnosis in the majority of patients and changed cancer-specific management 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.6
  • A study published in July 2013 looked at 157 specimens and compared accuracy for the Tissue of Origin test to immunohistochemistry stains (IHC). Overall, the accuracy of the Tissue of Origin Test was 89% versus 83% for IHC; Tissue of Origin was significantly more accurate (94%) than IHC-based diagnoses (79%) for poorly differentiated or undifferentiated samples. Further, the study showed that overall accuracy using IHC does not improve significantly after 1 round of IHC stains.7

* The Tissue of Origin test was previously known as the Pathwork® Tissue of Origin test.  Click here to access a complete list of publications that reference the Pathwork Tissue of Origin Test or CGI: Tissue of Origin Test.


 

Order a Test

Click here to order the Tissue of Origin.