Biomarkers in Carcinoma of Unknown Primary

Metastasis, the spread of neoplastic cells to secondary sites to form a mass, is a multistep process. In most of the cases, invasion of the tumor cells into the vascular wall and the circulation; attachment and invasion of the vascular lumen; extravasation to the new environment, “the metastatic site”; and forming a new colony are required. Each of these steps depends upon the success of molecular mechanisms, and, fortunately, only rare tumor cells are able to form metastasis. Epithelial-mesenchymal transition of the malignant cells, matrix metalloproteinases, and different proteases, stromal cells including the inflammatory cells, immune reaction and physical stress at the vasculature, attachment molecules, and epithelial transition of the tumor cells at the metastatic site are the participants.Many studies are focused on organ tropism of the cancer cells. Understanding mechanisms of metastasis is important for developing diagnostic algorithms and targeted therapies. Sometimes the metastatic mass is the presenting finding. In these cases finding the primary tumor is important. In some cases, instead of imaging and biochemical and histopathological findings, it is not possible. The histopathological biomarkers solve the primary origin in many cases. This chapter focuses on mechanisms of metastasis and description and frequency of primary unknown carcinomas.