PAEDIATRIC ONCOLOGY: EVOLUTION OF THE DIAGNOSTIC APPROACH

Key words: Childhood tumours, Diagnosis, Research progresses

The objective of cure for more than 70% of children with cancer outlines the successful routes built up by paediatric oncologists over the latest 40 years. This successful story stands for the development and evolution of the diagnostic routes where the clinical diagnosis of a paediatric tumour still represents a fundamental step. Indeed, as opposed to adult tumours, primary and secondary prevention do not work in paediatric oncology. Childhood tumours derive mainly from embryonic cells, i.e. undifferentiated resting stem cells, as opposed to adult tumours deriving generally from differentiated proliferating cells mainly of epithelial origin (carcinomas). As a consequence, the former cells lack of markers useful for their indirect identification, the latter cells need to enter processes of “de-differentiation”, which favour the production of more and more easily identifiable tumour markers (precocious diagnosis). Nevertheless, clinical diagnosis developed in strict conjunction with a number of research progresses in the fields of cytomorphology, immunophenotyping, cytogenetics and molecular genetics stands as a fundamental step. A precise identification of tumour cells by differential diagnosis is the first element of a successful treatment, since tumours show wide variation in response to specific therapies and their misdiagnosis can lead to suboptimal therapy. In recent years, knowledge of the molecular genetics of childhood cancers has been increasing at an exponential rate. The study of the molecular mechanisms of oncogenesis has led to an understanding of the role that tumour suppressors, oncogenes, and deoxyribonucleic acid (DNA) repair genes play in the development of the disease. Chromosomal translocations can lead to the disruption of growth regulatory genes and/or the formation of growth stimulatory fusion genes in leukaemias and some solid tumours. These alterations can occur sporadically or can be inherited, which often leads to cancer in children or young adults. Therefore, the development of more specific diagnostic tools, allowing a continuous reassessment of the bio-molecular features of paediatric tumours, has prompted important improvements of patients’ risk group definition in order to develop more and more targeted clinical trials. Finally, it is conceivable that the progress of our understanding of the molecular bases of the neoplastic transformation will open more opportunities to interfere directly with genes and their products altered inside the tumour cell.