Role of molecular diagnostics in determination of tissue of origin in Cancer of Unknown Primary (CUP)

Abstract

Cancer of unknown primary (CUP) is a condition seen in around 2–10% of patients with malignancy where the standard diagnostic workup fails to identify a specific tissue from which the tumor has arisen. As the survival of these patients is short, around 6–10 months, it becomes important to adopt newer technologies which aid in identifying the type of primary tumor so that the treatment can be guided based on the cancer type. Commonly used immunohistochemistry (IHC) panels may sometimes fail in providing a diagnosis as the CUP tissues contain usually either undifferentiated or dedifferentiate cells. Molecular cancer-classifier assay (MCCA) is an emerging diagnostic modality which is based on either gene expression profiling of the tumors or identification of epigenetic pattern of the tissues to make a probable diagnosis of the tissue from which the primary tumor may have arisen. Studies have shown that when tailored site-specific treatment was administered based on the outcomes of the MCCAs; an improvement in survival of the patients was seen. Recent NCCN guidelines suggest that the MCCAs should be used judiciously and on a case-to-case basis. The 2018 consensus statement from the Spanish Society of Pathology and the Spanish Society of Medical Oncology recognizes that the MCCAs are helpful when used to complement IHC, allowing for more accurate diagnosis of the primary site of tumor.