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

被引:14
作者
Celia Fernandez, Maria [1 ]
Martin, Ayelen [1 ]
Venara, Marcela [1 ]
de Lujan Calcagno, Maria [2 ]
Sanso, Gabriela [1 ]
Quintana, Silvina [3 ]
Chemes, Hector E. [1 ]
Barontini, Marta [1 ]
Pennisi, Patricia A. [1 ]
机构
[1] CEDIE CONICET Hosp Ninos Dr Ricardo Gutierrez, Ctr Invest Endocrinol, Buenos Aires, DF, Argentina
[2] Univ Buenos Aires, Fac Farm & Bioquim, Catedra Matemat, RA-1113 Buenos Aires, DF, Argentina
[3] Fares Taie Inst Anal, Mol Biol Lab, Mar Del Plata, Buenos Aires, Argentina
关键词
FACTOR-I RECEPTOR; MESENCHYMAL TRANSITION; GENE-MUTATIONS; EXPRESSION; CANCER; TUMOR; BENIGN; CARCINOMA; PROTEIN; TRAITS;
D O I
10.1111/cen.12205
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
ContextPheochromocytomas 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. ObjectiveTo analyse the distribution and expression of the IGF-1R in pheo/pgl of different genetic origin and degree of malignancy. MeasurementsWe 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). ResultsWe 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 117 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 60months and more than twofold higher at 120months of follow-up than in patients with intense IGF-1R labelling in their primary tumours. ConclusionsOur 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.
引用
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页码:623 / 630
页数:8
相关论文
共 39 条
  • [1] [Anonymous], WHO CLASSIFICATION T
  • [2] BASERGA R, 1995, CANCER RES, V55, P249
  • [3] The insulin-like growth factor-1 receptor as a target for cancer therapy
    Baserga, R
    [J]. EXPERT OPINION ON THERAPEUTIC TARGETS, 2005, 9 (04) : 753 - 768
  • [4] Clinical and genetic characteristics of patients with neurofibromatosis type 1 and pheochromocytoma
    Bausch, Birke
    Borozdin, Wiktor
    Neumann, Hartmut P. H.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (25) : 2729 - 2731
  • [5] Differential genetic alterations in von Hippel-Lindau syndrome-associated and sporadic pheochromocytomas
    Bender, BU
    Gutsche, M
    Gläsker, S
    Müller, B
    Kirste, G
    Eng, C
    Neumann, HPH
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (12) : 4568 - 4574
  • [6] SDHA is a tumor suppressor gene causing paraganglioma
    Burnichon, Nelly
    Briere, Jean-Jacques
    Libe, Rossella
    Vescovo, Laure
    Riviere, Julie
    Tissier, Frederique
    Jouanno, Elodie
    Jeunemaitre, Xavier
    Benit, Paule
    Tzagoloff, Alexander
    Rustin, Pierre
    Bertherat, Jerome
    Favier, Judith
    Gimenez-Roqueplo, Anne-Paule
    [J]. HUMAN MOLECULAR GENETICS, 2010, 19 (15) : 3011 - 3020
  • [7] Cyclooxygenase-2 expression correlates with phaeochromocytoma malignancy: evidence for a Bcl-2-dependent mechanism
    Cadden, I. S.
    Atkinson, A. B.
    Johnston, B. T.
    Pogue, K.
    Connolly, R.
    McCance, D.
    Ardill, J. E. S.
    Russell, C. F.
    McGinty, A.
    [J]. HISTOPATHOLOGY, 2007, 51 (06) : 743 - 751
  • [8] IGF-I Regulates Pheochromocytoma Cell Proliferation and Survival In Vitro and In Vivo
    Celia Fernandez, Maria
    Venara, Marcela
    Nowicki, Susana
    Chemes, Hector E.
    Barontini, Marta
    Pennisi, Patricia A.
    [J]. ENDOCRINOLOGY, 2012, 153 (08) : 3724 - 3734
  • [9] Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma
    Comino-Mendez, Inaki
    Gracia-Aznarez, Francisco J.
    Schiavi, Francesca
    Landa, Inigo
    Leandro-Garcia, Luis J.
    Leton, Roco
    Honrado, Emiliano
    Ramos-Medina, Rocio
    Caronia, Daniela
    Pita, Guillermo
    Gomez-Grana, Alvaro
    de Cubas, Aguirre A.
    Inglada-Perez, Lucia
    Maliszewska, Agnieszka
    Taschin, Elisa
    Bobisse, Sara
    Pica, Giuseppe
    Loli, Paola
    Hernandez-Lavado, Rafael
    Diaz, Jose A.
    Gomez-Morales, Mercedes
    Gonzalez-Neira, Anna
    Roncador, Giovanna
    Rodriguez-Antona, Cristina
    Benitez, Javier
    Mannelli, Massimo
    Opocher, Giuseppe
    Robledo, Mercedes
    Cascon, Alberto
    [J]. NATURE GENETICS, 2011, 43 (07) : 663 - U189
  • [10] de Krijger RR, 1999, J PATHOL, V188, P51