title: New strategies for carcinoma of unknown primary: the role of tissue-of-origin molecular profiling.
abstract: The taxonomy and management of carcinoma of unknown primary (CUP) has matured over the past decade with the use of sophisticated imaging and pathologic tools. In the era of tailored therapeutics, this presents both an opportunity and a challenge. Tissue-of-origin (ToO) molecular profiling has an important role in the diagnostic armamentarium of CUP cancers, and its niche continues to evolve with ongoing prospective studies. Despite the inability to conduct direct validation (i.e., primary tumor), the use of the indirect validation methods with immunohistochemistry (IHC), imaging, and treatment response has allowed us to evaluate the performance accuracy of ToO profiling assays in CUP cancers. Despite advances, we struggle with the undifferentiated neoplasms, which often remain unclassifiable after an exhaustive use of IHC and ToO profiling assays. Genomic characterization of these and other select CUP cancers using next-generation sequencing techniques may reveal actionable biomarkers outside the (tissue specific) cellular framework. Also, going forward, using data from comparative effectiveness research, one could envision using a streamlined, cost-effective algorithm that integrates IHC and ToO molecular profiling in patients with limited (or difficult-to-access) biopsies and difficult-to-diagnose cancers.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. gvaradha@mdanderson.org
authors.forename: Gauri
authors.initials: G
authors.lastname: Varadhachary
mesh_terms: D001706:Biopsy; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016896:Treatment Outcome