title: Overexpression of the insulin-like growth factor 1 receptor (IGF-1R) is associated with malignancy in familial pheochromocytomas and paragangliomas.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Centro de Investigaciones Endocrinológicas, CEDIE-CONICET. Hospital de Niños Dr. R. Gutierrez, Buenos Aires, Argentina.
authors.forename: María Celia
authors.initials: MC
authors.lastname: Fernandez
authors.forename: Ayelen
authors.initials: A
authors.lastname: Martin
authors.forename: Marcela
authors.initials: M
authors.lastname: Venara
authors.forename: María de Luján
authors.initials: Mde L
authors.lastname: Calcagno
authors.forename: Gabriela
authors.initials: G
authors.lastname: Sansó
authors.forename: Silvina
authors.initials: S
authors.lastname: Quintana
authors.forename: Héctor E
authors.initials: HE
authors.lastname: Chemes
authors.forename: Marta
authors.initials: M
authors.lastname: Barontini
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Pennisi
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000378:metabolism* / Q000473:pathology*; D010673:Pheochromocytoma / Q000378:metabolism* / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D017526:Receptor, IGF Type 1