Tissue of Origin Test Determines Primary Tumor Site

The tissue of origin test indicated a probable origin of metastatic cancer of unknown origin (CUP) in 73% of tumors tested. The test uses a microarray to measure the expression pattern comprising more than 1,500 genes in the tumor, and compares it to the expression patterns of a panel of 15 known tumor types representing 60 morphologies overall to help determine the tumor's origin.

The tissue of origin test was validated and cleared by the U.S. Food and Drug Administration (FDA; Rockville, MD, USA) using metastatic tumors for which the primary site was known.

Cancer of unknown origin cases account for approximately 3% of all malignancies, representing one of the 10 most frequent cancer diagnoses. The CUP samples used in this study consisted of 11 fresh-frozen tumor specimens from the Mayo Clinic (Rochester, MN, USA) whose origin could not be determined after full clinical and imaging workup, including immunohistochemistry (IHC). Cases where the tissue of origin was identified have treatment options that show increased survival compared to standard therapies used for the treatment of CUP.

Pathwork Diagnostics (Sunnyvale, CA, USA), a molecular diagnostics company focused on oncology, presented the study involving the gene-expression based Pathwork tissue of origin test at the Association for Molecular Pathology (AMP) annual meeting, which was held in Gaylord, TX (USA), from October 29-November 2, 2008. The company presented two additional studies involving the tissue of origin test.

In the first study, Dr. Catherine Dumur, Ph.D., director of molecular morphology genomics for the department of pathology, Virginia Commonwealth University School of Medicine (Richmond, VA, USA), performed a clinical verification comparing the results from the Pathwork tissue of origin test to the original pathology report diagnoses in 23 poorly differentiated and undifferentiated tumors, including one CUP specimen. Overall, the tissue of origin test demonstrated 94.7 % accuracy. In cases of disagreement, the test results were compared to IHC and imaging results. Upon further review of the IHC and computed tomography (CT) scans results, four of the five cases that initially showed a disagreement between the original diagnosis and the Pathwork tissue of origin test revealed that that the test was correct. This study supports the hypothesis that the Pathwork test can be effectively used to complement existing diagnostic technologies for tissue of origin analysis.

In the second study, Dr. Dumur assessed how variations in clinical specimen acquisition affected the test's accuracy and reproducibility. Her results demonstrated that with proper sample handling and rigorous quality control procedures for RNA extraction and microarray analysis, tumor classification utilizing the tissue of origin test was not adversely affected.

"Identifying the tumor's origin can allow oncologists to prescribe more appropriate, targeted therapy and avoid the toxicity of less-specific chemotherapies. They may also be able to enroll these patients in new therapeutic clinical trials, which otherwise would not be available without a defined tissue of origin,” said David Henner, M.D., Ph.D., CMO of Pathwork Diagnostics.

Related Links:
U.S. Food and Drug Administration
Mayo Clinic
Pathwork Diagnostics
Virginia Commonwealth University School of  Medicine