Molecular Profiling in Unknown Primary Cancer: Accuracy of Tissue of Origin Prediction

Introduction. This retrospective, multi‐institutional study evaluated the accuracy of tissue‐of‐origin prediction by molecular profiling in patients with carcinoma of unknown primary site (CUP). Methods. Thirty‐eight of 501 patients (7.6%) with CUP, seen in 2000–2008, had their latent primary site tumor subsequently identified during life. Twenty‐eight of these patients (73.7%) had adequate initial tissue biopsies available for molecular profiling with a reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay (Cancer Type ID; bioTheranostics, Inc., San Diego, CA). The assay was performed on formalin‐fixed paraffin‐embedded biopsy specimens in a blinded fashion, and the assay results were compared with clinicopathologic data and the actual latent primary sites. Results. Twenty of the 28 (71.4%) RT‐PCR assays were successfully completed (eight biopsies had either insufficient tumor or poorly preserved RNA). Fifteen of the 20 assay predictions (75%) were correct (95% confidence interval, 60%–85%), corresponding to the actual latent primary sites identified after the initial diagnosis of CUP. Primary sites correctly identified included breast (four patients), ovary/primary peritoneal (four patients), non‐small cell lung (three patients), colorectal (two patients), gastric (one patient), and melanoma (one patient). Three predictions were incorrect (intestinal, testicular, sarcoma) in patients with gastroesophageal, pancreatic, and non‐small cell lung cancer, respectively, and two were unclassifiable in patients with non‐small cell lung cancer. Clinicopathologic findings were helpful in suggesting the correct primary site in some patients and appear to complement the molecular assay findings. Conclusions. These data validate the reliability of this assay in predicting the primary site in CUP patients and may form the basis for more successful site‐directed therapy, when used in concert with clinicopathologic data. The authors evaluated the accuracy of tissue‐of‐origin prediction by molecular profiling in patients with carcinoma of unknown primary site. They found the Cancer Type ID assay (bioTheranostics, Inc.) to be reliable in predicting the primary site in patients with carcinoma of unknown primary, and suggest that this could form the basis for more successful site‐directed therapy when used in concert with clinicopathologic data.