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.
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.
Authors: Hugo M Horlings; Ryan K van Laar; Jan-Martijn Kerst; Helgi H Helgason; Jelle Wesseling; Jacobus J M van der Hoeven; Marc O Warmoes; Arno Floore; Anke Witteveen; Jaana Lahti-Domenici; Annuska M Glas; Laura J Van't Veer; Daphne de Jong Journal: J Clin Oncol Date: 2008-09-20 Impact factor: 44.544
Authors: M B Hannouf; E Winquist; S M Mahmud; M Brackstone; S Sarma; G Rodrigues; P K Rogan; J S Hoch; G S Zaric Journal: Curr Oncol Date: 2017-10-25 Impact factor: 3.677
Authors: M B Hannouf; E Winquist; S M Mahmud; M Brackstone; S Sarma; G Rodrigues; P Rogan; J S Hoch; G S Zaric Journal: Pharmacogenomics J Date: 2016-03-29 Impact factor: 3.550
Authors: Anne Kirstine H Møller; Annika Loft; Anne K Berthelsen; Karen D Pedersen; Jesper Graff; Charlotte B Christensen; Junia C Costa; Lene T Skovgaard; Katharina Perell; Bodil L Petersen; Gedske Daugaard Journal: Oncologist Date: 2012-06-18
Authors: G R Varadhachary; S Karanth; W Qiao; H R Carlson; M N Raber; J D Hainsworth; F A Greco Journal: Int J Clin Oncol Date: 2013-06-28 Impact factor: 3.402
Authors: Charles R Handorf; Anand Kulkarni; James P Grenert; Lawrence M Weiss; William M Rogers; Oliver S Kim; Federico A Monzon; Meredith Halks-Miller; Glenda G Anderson; Michael G Walker; Raji Pillai; W David Henner Journal: Am J Surg Pathol Date: 2013-07 Impact factor: 6.394