CUP represents a group of biologically and clinically heterogenous tumors. Management of patients with CUP requires a truly multi-disciplinary approach and close communications between the pathologists and oncologists to ensure an effective work-up. A variety of clonality analysis methodologies can be employed to determine a site of origin for the metastatic lesion. Gene and protein expression profiling technologies are potentially of great benefit in the identification of a primary tumor and may aid in the accurate assessment of prognosis. The identification of CUP-specific molecular signatures may offer new avenues for diagnosis and treatment.
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