How to hunt for a primary tumour site

An educational session explored a range of options that clinicians could adopt to manage cancer patients where the primary tumour site is unknown.

Moderators, Professor Nicholas Pavlidis from the University of Ioannina, Greece, and Professor Ahmad Awada from Institut Jules Bordet, Brussels, Belgium, reminded the audience that cancers of unknown primary origin (CUP) represent the 7th to 8th most frequent type of cancer and the 4th most common cause of cancer death. They also stressed that there is no set of rules to follow in these difficult cases and so an integrated approach would be needed in order to gather a wide range of data and information to piece together an optimal management plan.

Dr Karin Oien from the University of Glasgow, UK, provided information on the diagnostic approaches available to the clinician, starting from basic immunohistochemistry (IHC) and working-up to full molecular profiling. She suggested that molecular profiling could contribute towards the diagnosis of poorly differentiated and/or metastatic tumours, especially where morphology and IHC are equivocal or conflicting, in cases where diagnosis includes multiple possible differentials or when tissue or time is limited. However, she warned that profiling results should be evaluated in the context of pathological and clinical findings and that molecular profiling is not currently recommended by ESMO’s Clinical Practice Guidelines.

Dr George Pentheroudakis, also from the University of Ioannina, described the genetic mutations and cell signaling pathways that are frequently reported in CUP. “CUP is a heterogeneous group of tumours,” he advised, “expression of the oncoproteins, c-myc, ras, human epidermal growth factor receptor 2 (HER2) and Bcl2 are common, but overexpression is rare”, he added.

Dr Pentheroudakis’ talk was followed by insights from his colleague, Professor Pavlidis, on a framework for optimising the therapeutic management of patients with distinct clinical pathological CUP subsets.