Lymph node extracapsular extension as a marker of aggressive phenotype: Classification, prognosis and associated molecular biomarkers

Lymph node extracapsular extension, also termed extranodal extension or extracapsular spread (ECS) from lymph nodes, is a key characteristic of aggressive phenotype in cancer, carrying a major impact on prognosis. Controversy exists with regards the classification of ECS by different histopathological assessment methods published in the literature. Whilst much focus has been placed on ECS in the setting of head and neck cancer, numerous studies also highlight its significance in a range of other malignancies, including a wide range of gastrointestinal malignancies. Prognostically, the presence of ECS broadly negatively impacts on disease recurrence and survival, with a greater range of studies now demonstrating how the nature and extent of ECS influences disease outcomes. Molecular techniques such as DNA sequencing and immunohistochemistry have identified molecular biomarkers associated with ECS. Knowledge of these biomarkers will help guide future broader studies. Technological advancements resulting from the recent -omics revolution and utilising an early, wide-ranging, and integrated approach, provide the prospect of improved identification of biomarkers associated with aggressive phenotype. These approaches may validate existing putative biomarkers or identify novel independent prognostic and predictive biomarkers, facilitating a future personalized medicine approach.