Overexpression of the insulin-like growth factor 1 receptor (IGF-1R) is associated with malignancy in familial pheochromocytomas and paragangliomas

Context Pheochromocytomas and paragangliomas (pheo/pgl) are neuroendocrine tumours derived from chromaffin cells. Although mostly benign, up to 26% of pheo/pgl will undergo malignant transformation. Reliable histological signs to differentiate benign pheo/pgl from malignant tumours are currently lacking. Increased IGF‐1R expression has been shown during progression to metastatic phenotypes of several types of cancer. Objective To analyse the distribution and expression of the IGF‐1R in pheo/pgl of different genetic origin and degree of malignancy. Measurements We studied the expression of the IGF‐1R protein by immunohistochemistry, in 40 primary tumours from patients with pheo/pgl from different genetic aetiology (11 of 29 metastatic/nonmetastatic diseases). Results We found a strong association between increased expression of IGF‐1R and malignant behaviour regardless of the age at diagnosis and the genetic aetiology. IGF‐1R labelling was mostly weak in primary tumours from patients with nonmetastatic pheo/pgl. Conversely, intense IGF‐1R labelling was predominant in cases of pheo/pgl with confirmed metastatic disease. The risk of metastases was 11·7 times higher if tumour IGF‐1R labelling was intense independently of age at diagnosis. The probability of remaining free of metastases was higher in patients with pheo/pgl scored weak for IGF‐1R at 60 months and more than twofold higher at 120 months of follow‐up than in patients with intense IGF‐1R labelling in their primary tumours. Conclusions Our results strongly suggest that IGF‐1R is associated with malignancy in familial pheo/pgl and that IGF‐1R expression in the primary tumour might be a useful tool to detect those patients harbouring pheo/pgl who have an increased risk of metastasis.