Microarray-based Gene Expression Testing for Cancers of Unknown Primary
DESCRIPTION
Cancers of unknown primary or occult primary malignancies are tumors that have metastasized from an unknown primary source, and make up approximately 2% - 6% of all cancer cases in the United States.
Conventional methods used to aid in the identification of the origin of a cancer of unknown primary malignancy include a thorough history and physical examination, computed tomography (CT) scans of the chest, abdomen, and pelvis, routine laboratory studies; and targeted evaluated of specific signs and symptoms. Identifying the primary origin of a tumor can dictate cancer specific treatment, expected outcome, and prognosis.
Microarray-based gene expression testing (e.g., the Pathwork® Tissue of Origin Test), also known as gene expression profiling, is being offered by the manufacturer as being possibly useful in identifying the origin of cancers of unknown primary malignancy. The test measures the expression of more than 1,500 genes and compares the similarity of the gene expression profile of a cancer of unknown primary to a database of known profiles from 15 tissues with more than 60 histologic morphologies. The test uses a proprietary Pathchip® microarray and runs on the Affymetrix GeneChip® system. The report generated for each tumor consists of a similarity score, which is a measure of similarity of the gene expression profile of the specimen to the profile of the 15 known tumors in the database. Scores range from 0 (very low similarity) to 100 (very high similarity), and sum to 100 across all 15 tissues on the panel. If a single similarity score is greater than or equal to 30, it indicates that this is likely the tissue of origin. If every similarity score is between 5 and 30, the test result is considered indeterminate, and a similarity score of less than 5 rules out that tissue type as the likely origin.
The Pathwork® Tissue of Origin Test received clearance for marketing through the U. S. Food and Drug Administration’s (FDA) 510(k) process in July 2008. The test is intended to measure the degree of similarity between the RNA expression pattern in a patient’s fresh-frozen tumor and the RNA expression patterns in a database of tumor samples (poorly differentiated, undifferentiated, and the metastatic cases) that were diagnosed according to then-current clinical and pathological practice. It is intended for use in the context of the patient’s clinical history and other diagnostic tests evaluated by a qualified clinician. Test approval was granted with the following limitations. This test is not intended:
To establish the origin of tumors that cannot be diagnosed according to current clinical and pathological practice (e.g., carcinoma of unknown primary)
To subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice
To predict disease course, survival, or treatment efficacy
To distinguish primary from metastatic tumors
POLICY
Microarray-based gene expression testing, including, but not limited to, the following indications is considered investigational:
To measure the degree of similarity between the RNA expression pattern in a fresh frozen tumor and a database of tumor samples (poorly differentiated, undifferentiated, and metastatic cases) that were diagnosed according to then-current clinical and pathological practice
To establish the origin of tumors that cannot be diagnosed according to current clinical and pathological practice (e.g., carcinoma of unknown primary)
To subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice
To predict disease course, survival, or treatment efficacy
To distinguish primary from metastatic tumors
IMPORTANT REMINDER
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ADDITIONAL INFORMATION
Clinical trials have not been conducted that provide direct evidence of the clinical outcomes (clinical utility) of microarray-based gene expression testing (e.g., the Pathwork® Tissue of Origin test). The clinical application of gene expression profiling to direct patient management and tumor site-specific therapy also has not been demonstrated in prospective studies. Therefore, the impact of this testing on clinical outcomes is not currently known.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (11:2010). Microarray-based gene expression testing for cancers of unknown primary (2.04.54). Retrieved May 18, 2011 from BlueWeb. (13 articles and/or guidelines reviewed)
Dumar, E. I., Lyons-Weiler, M., Sciulli, C., Garrett, C. T., Schrijver, I., Holley, T. K., et al. (2008). Journal of Molecular Diagnostics, 10 (1), 67-77. (Level 2 Evidence - Industry sponsored)
Monzon, F. A., Lyons-Weiler, M., Buturovic, L. J., Rigl, C. T., Henner, W. D., Sciulli, C., et al. (2009). Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. Journal of Clinical Oncology, 27 (15), 2503-2508. (Level 2 Evidence - Industry sponsored)
Monzon, F. A., Medeiros, F., Lyons-Weiler, M., & Henner, W. D. (2010). Identification of tissue of origin in carcinoma of unknown primary with a microarray-based gene expression test. Diagnostic Pathology 5 (3). Retrieved May 23, 2011 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823680/?tool=pubmed. (Level 2 Evidence - Industry sponsored)
National Comprehensive Cancer Network. (2011, February), NCCN clinical practice guidelines in oncology™. Occult Primary (cancer of unknown primary, [CUP]) (V.2.2011). Retrieved May 23, 2011 from http://www.nccn.org/professionals/physician_gls/pdf/occult.pdf.
National Institute for Health and Clinical Excellence (NICE). National Collaborating Centre for Cancer. (2010, July). Diagnosis and management of metastatic malignant disease of unknown primary origin. Downloaded May 25, 2011 from http://www.nice.org.uk/nicemedia/live/13044/49864/49864.pdf.
U. S. Food and Drug Administration. (2008, July). Center for Devices and Radiological Health. 510(k) substantial equivalence determination. Retrieved May 25, 2011 from http://www.accessdata.fda.gov/cdrh_docs/reviews/K080896.pdf.
U. S. Food and Drug Administration. (2010, June). Center for Devices and Radiological Health. 510(k) substantial equivalence determination. Retrieved May 25, 2011 from http://www.accessdata.fda.gov/cdrh_docs/reviews/K092967.pdf.
Wu, A. H., Drees, J. C., Wang, H., VandenBerg, S. R., Lal, A., Henner, W. D., et al. (2010). Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers. Diagnostic Pathology, 5 (26). Retrieved May 23, 2011 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867958/?tool=pubmed. (Level 2 Evidence - Industry sponsored)
ORIGINAL EFFECTIVE DATE: 11/14/2009
MOST RECENT REVIEW DATE: 10/8/2011
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