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Molecular Diagnosis of the Tissue of Origin in Cancer of Unknown Primary Site: Useful in Patient Management

  • Tissue of Origin (JM Cates, Section Editor)
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Opinion Statement

Cancer of unknown primary site (CUP) is a clinicopathologic syndrome consisting of many types of cancer and accounting for approximately 3 % of all patients with advanced cancers. This syndrome has frustrated patients and physicians for decades, because a primary site or tissue of origin has not been possible to identify clinically, despite the presence of metastatic tumor. Favorable subsets (approximately 20 % of all CUP) with a presumptive occult primary site have been recognized for several decades based on clinical and standard pathologic features; site-specific therapy in these patients improves their survival compared with the majority of other (approximately 80 %) CUP patients. These other patients, most with adenocarcinomas, have been difficult to treat because the tissue of origin was unknown. Broad-spectrum empiric chemotherapy became the standard approach for these patients in the past 30 years. More recently, new diagnostic technology (evolving immunohistochemistry and emergent gene-expression profiling) has enabled us to establish accurately a tissue of origin in most (90 %+) CUP patients. Gene-expression profiling assays complement standard pathology and for the majority of biopsy specimens accurately identify the primary site or tissue of origin; clinical studies have supported the value of site-directed therapy. When the tissue of origin is in doubt after standard pathologic examination, a gene expression assay is frequently diagnostic, and the outcome of many CUP patients is improved with site-specific therapy. The era of empiric therapy has ended in favor of site-specific therapy, based on the precise diagnosis of the tumor type present in each patient.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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  1. Sarah Cannon Cancer Center and Research Institute, Tennessee Oncology, PLLC, 250 25th Avenue North Suite 100, Nashville, TN, 37203, USA

    F. Anthony Greco MD

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  1. F. Anthony Greco MD
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Correspondence to F. Anthony Greco MD.

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Greco, F.A. Molecular Diagnosis of the Tissue of Origin in Cancer of Unknown Primary Site: Useful in Patient Management. Curr. Treat. Options in Oncol. 14, 634–642 (2013). https://doi.org/10.1007/s11864-013-0257-1

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