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

FERNANDEZ, MARÍA CELIA; MARTÍN, AYELEN; VENARA MARCELA; CALCAGNO MARÍA DE LUJAN; SANSO G; QUINTANA SILVINA; CHEMES HECTOR; BARONTINI MARTA; PENNISI PATRICIA A

CLINICAL ENDOCRINOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2013 vol. 79 p. 623 - 630

0300-0664

>Context: Pheochromocytomas and paragangliomas (pheo/pgl) are neuroendocrine tumors 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 tumors are currently lacking. Increased IGF-1R expression has been shown during progression to metastatic phenotypes of several types of cancer. Objective: to analyze 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 tumors from patients with pheo/pgl from different genetic etiology (11/29 metastatic/non-metastatic disease). Results: We found a strong association between increased expression of IGF-1R and malignant behavior regardless the age at diagnosis and the genetic etiology. IGF-1R labeling was mostly weak in primary tumors from patients with non-metastatic pheo/pgl. Conversely, intense IGF-1R labeling was predominant in cases of pheo/pgl with confirmed metastatic disease. The risk of metastases was 11.7 times higher if tumor IGF-1R labeling 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 two fold higher at 120 months of follow-up than in patients with intense IGF-1R labeling in their primary tumors. Conclusions: Our results strongly suggest that IGF-1R is associated with malignancy in familial pheo/pgl and that IGF-1R expression in the primary tumor might be a useful tool to detect those patients harboring pheo/pgl that have an increased risk of metastasis.