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Molecular Profiling of Carcinoma of Unknown Primary and Correlation With Clinical Evaluation

Gauri R. Varadhachary, Dmitri Talantov, Martin N. Raber, Christina Meng, Kenneth R. Hess, Tim Jatkoe, Renato Lenzi, David R. Spigel, Yixin Wang, F. Anthony Greco, James L. Abbruzzese, John D. Hainsworth

From The University of Texas M. D. Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston TX; Sarah Cannon Research Institute and Tennessee Oncology, Nashville TN; and Veridex, La Jolla, CA

Corresponding author: John D. Hainsworth, MD, Sarah Cannon Research Institute, 250 25th Ave North, Suite 110, Nashville, TN 37203; e-mail: jhainsworth{at}tnonc.com

Purpose To evaluate the feasibility of a 10-gene reverse transcriptase polymerase chain reaction assay to identify the tissue of origin in patients with carcinoma of unknown primary (CUP) site.

Patients and Methods Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 120 patients with CUP were collected retrospectively from Sarah Cannon Research Institute, Nashville, TN, and prospectively from The University of Texas M. D. Anderson Cancer Center, Houston, TX. Tissue of origin assignments by the assay were correlated with clinical and pathologic features and with response to therapy.

Results The assay was successfully performed in 104 patients (87%), and a tissue of origin was assigned in 63 patients (61%). In the remaining 41 patients (39%), the molecular profiles were not specific for the six tumor types detectable by this assay. The tissues of origin most commonly identified were lung, pancreas, and colon; most of these patients had clinical and pathologic features consistent with these diagnoses. Patients with lung and pancreas profiles had poor response to treatment. Patients with colon cancer profiles had better response to colon cancer–specific therapies than they did to empiric CUP therapy with taxane/platinum regimens. Patients with ovarian cancer profiles were atypical, with widespread visceral metastases and a paucity of overt peritoneal involvement.

Conclusion This gene expression profiling assay was feasible using FFPE biopsy specimens and identified a putative tissue of origin in 61% of patients with CUP. In most patients, the assigned tissue of origin was compatible with clinicopathologic features and response to treatment. Prospective studies in which assay results are used to direct therapy are indicated.

Supported in part by grants from Veridex and the Minnie Pearl Cancer Foundation.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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