Adding variables to complexity. Molecular imaging and molecular biology: a no-longer-secret liaison in NETs

Abstract

Neuroendocrine tumours (NETs) are a challenging model for both researchers and clinicians. NETs comprise a very heterogeneous family of tumours: they are rare but with an increasing incidence, indolent lesions but often metastatic at the time of diagnosis, secreting or not, and sometimes very small and sometimes very large. Their high clinical complexity and wide biological diversity, and the restricted diagnostic armamentarium (including limited imaging resolution and lack of reliable biomarkers), make diagnostic flow charts and treatments uncertain in NET patients. A multidisciplinary and integrated approach is the only way to improve the management of these patients. The tumour grading according to histopathology (e.g. Ki67) is widely accepted as a prognostic factor. However, correlation with in vivo functional imaging by PET (metabolism, proliferation, receptors) is not always found, and findings are discordant. Researchers and clinicians are working together to develop more reproducible prognostic factors and markers of response to therapy and recurrence. Within this context, the work by Bodei et al. develops new and interesting perspectives [1].Cancer is a multifactorial disease whose development and progression are affected by intrinsic genetic and molecular features, by the host environment and by their reciprocal interplay. In this regard, cancer may be considered as a nonlinear, open, and intrinsically dynamic system of interconnected and mutually dependent components. Every element participates in the construction of the system and is tightly interconnected with the others. It is now becoming evident that a reductionist approach, in which one or few selected variables are analysed to explain or predict disease status, is largely insufficient to address the complexity of the Bcancer system^. A strong rationale exists to believe that there is a direct link between molecular imaging and molecular biology of tumours. The degree of uptake of a radioactive tracer as measured in PET is a reflection of tumour metabolism and is a direct consequence of the molecular properties of the tumour. As the use of PET in the clinical management of cancer patients is becoming a standard widely available technique, some investigators have explored the correlation between SUV and gene expression.Osborne et al. investigated the possible correlation between 18 F-FDG uptake and estrogen receptor (ER) status and gene expression profile of locally invasive breast cancer. They found that high SUV correlates with ER-negative status and with the expression of genes associated with increased glucose metabolism [2]. In liver cancer, high 18 F-FDG uptake has been shown to correlate with increased expression of genes involved in cell adhesion, motility and metastasis [3], while in giant cell tumours, high 18 F-FDG accumulation correlates with the expression of genes involved in angiogenesis and cell proliferation [4]. The evidence from these studies provides a partial explanation for the prognostic value of 18 F-FDG SUV and emphasizes...