The primary site cannot be found after clinical and pathological evaluation, which are called cancers of unknown primary origin (CUP). CUPs may resemble a specific primary tumor site which shares common clinicopathological characteristics and prognosis. However, it may be present as a distinct disease entity with undifferentiated pathological features. More than 4% of patients are diagnosed as CUP. These patients were diagnosed as malignant tumors by cytology or pathology. And they were usually treated with empirical chemotherapy and associated with a poor prognosis. How to accurately diagnose and treat a cancer of unknown primary origin is a major clinical concern. To address this question, a complex assessment is carried out which includes a complete medical history of the patient, physical examination, complete blood count, urinalysis, serum chemistries, histologic evaluation, chest radiograph, computed tomography, magnetic resonance imaging, and immunohistochemistry (IHC) studies. Molecular diagnostic information reflects that CUP's molecular characteristics are similar to primary tumors with the development of genomics and the expansion of gene sequencing technology. Gene expression profiling is the most commonly used molecular diagnostic method for CUP. In this chapter, we summarize the current diagnostic methods and challenges of CUP, and the clinical value of the molecular-level tumor diagnostic technique.
Keywords: Cancers of unknown primary origin; Gene expression profiling; Immunohistochemistry; Metastasis; Molecular diagnostics.