Molecular Tumor Profiling in the Diagnosis of Patients with Carcinoma of Unknown Primary Site: Retrospective Evaluation of Gene Microarray Assay
- *Corresponding Author:
- John D. Hainsworth, MD
Chief Scientific Officer, Sarah Cannon Research Institute
3322 West End, Avenue, Suite 900, Nashville, TN 37203, USA
E-mail: [email protected], [email protected]
Received Date: February 15, 2011; Accepted Date: June 20, 2011; Published Date: June 27, 2011
Citation: Hainsworth JD, Pillai R, Henner WD, Halks-Miller M, Lane CM, et al. (2011) Molecular Tumor Profiling in the Diagnosis of Patients with Carcinoma of Unknown Primary Site: Retrospective Evaluation of Gene Microarray Assay. J Mol Biomark Diagn 2:106. doi:10.4172/2155-9929.1000106
Copyright: © 2011 Hainsworth JD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Molecular tumor profiling has potential importance in identifying the tissue of origin in patients with cancer of unknown primary (CUP). We retrospectively performed the Tissue of Origin test, an FDA-cleared commercially available gene microarray assay, on biopsy specimens from patients with CUP. Assay results were correlated with clinical and pathologic features, and with previous results using the Veridex 10-gene CUP assay, a molecular RT-PCR assay designed to detect 6 primary sites. Methods: Archival formalin-fixed, paraffin-embedded biopsy specimens from 48 patients with CUP were tested. The assay results were reported without incorporation of clinicopathologic information except biopsy site and patient gender. The assay results were correlated with clinicopathologic information, treatment results, and with results of the previously performed Veridex assay. Results: The Tissue of Origin test was successfully performed in 45 tumor specimens. In 43 of 45 assays (96%), a specific tissue of origin was predicted. The most commonly identified tissues of origin included: lung (11), pancreas (6), sarcoma (6), ovary (5), and colon (4). Most diagnoses were compatible with the clinical features, IHC staining, and response to treatment. The finding of 6 sarcomas was unusual in this patient population and was suggested by routine pathology in only 1 patient. The Tissue of Origin test provided predictions in a higher percentage of patients than did the Veridex CUP assay (96% versus 53%). However, concordance between assay results was relatively low. Conclusions: The Tissue of Origin test provided predictions of the primary site in 96% of patients with CUP. Predictions were generally consistent with clinicopathologic features. Agreement between the Tissue of Origin test and the Veridex CUP assay was relatively low, possibly related to the limited number of genes assessed by the Veridex CUP assay. Additional trials are necessary to confirm the value of these assays in patient management. Carcinoma of unknown primary site (CUP) is a relatively common clinical syndrome, accounting for approximately 2-5% of all cancer diagnoses. Although several clinical subsets with specific treatment implications have been identified, the majority of patients receive empiric chemotherapy which is only modestly effective, producing median survivals of 9-11 months [1-3]. As treatments improve for specific cancer types, it becomes more important to identify the tissue of origin in patients with CUP so that site-specific treatment can be administered. During the last several years, specific gene expression profiles based on the tissue of origin have been identified for many tumor types [4-6]. Several diagnostic assays, based on either gene microarray or reverse transcriptase polymerase chain reaction (RT-PCR) technology have been developed as an aid to tumor identification based on specific gene expression profiles. The ability to perform these assays on formalinfixed, paraffin-embedded archival tissue specimens broadens their potential applicability in the diagnosis of patients with CUP. The Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA) is a microarray-based gene expression assay for determining the similarity of a tumor specimen to 15 known tumor tissue types. In a group of 462 cancer patients, this assay accurately predicted the primary site in 89% when performed on biopsy specimens from metastatic sites or poorly differentiated primaries . In the current study, we retrospectively performed the Tissue of Origin Test on a group of 48 patients with CUP, and correlated these results with clinical features, standard pathology results, and response to treatment. In addition, we compared the results of the Tissue of Origin Test with previous results obtained with the Veridex 10-gene assay, an RT-PCR assay also developed for this purpose.