Molecular profiling in unknown primary cancer: accuracy of tissue of origin prediction

Oncologist. 2010;15(5):500-6. doi: 10.1634/theoncologist.2009-0328. Epub 2010 Apr 28.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / diagnosis*
  • Carcinoma / drug therapy
  • Carcinoma / genetics
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / diagnosis*
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome