Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma

Mod Pathol. 2011 Feb;24(2):201-8. doi: 10.1038/modpathol.2010.191. Epub 2010 Nov 5.


The biology of breast carcinoma shows a great variation, reflected by the recent classification of phenotypes based on DNA microarrays or immunohistochemistry. The aim of this study was to determine the prevalence of insulin-like growth factor-1 receptor (IGF1R) in breast carcinoma subtypes and the impact on the outcome. We studied 197 consecutive breast carcinoma patients in stage I-II treated conservatively. Phenotypes were assessed on the basis of the expressions of ER/PR, HER2, Ki67, p53, Bcl2, CK5/6 and EGFR. Moreover, IGF1R expression (α-subunit and β-phosphorylated/active form) was evaluated by immunohistochemistry, IGF1R mRNA levels by quantitative RT-PCR and IGF1R mutations by direct DNA sequencing. Overall, 40% (78/197) of tumors were luminal A, 24% (48/197) luminal B, 19% (37/197) HER2-positive and 17% (34/197) basal/triple-negative. Luminal A tumors were predominantly of low grade, without necrosis, presenting in older patients as a ≤2-cm unilateral mass (all P ≤ 0.046). α-IGF1R overexpression was observed more frequently in luminal A (49%) cases, followed by luminal B (20%), HER2-positive area under the curve (22%) and basal/triple-negative cases (9%) (P = 0.01) with similar results for mRNA levels (53, 24, 13 and 10%, respectively) (P = 0.038), but without differences for mutations (P = NS). High IGF1R mRNA correlated with poor patient survival among subtypes (P = 0.004) (Kaplan-Meier; log-rank test). For overall survival, only histological grade and IGF1R mRNA emerged as significant predictors (P ≤ 0.034; Cox regression). Increased IGF1R mRNA implies poorer patient prognosis among the different subtypes, and that may be associated with the lack of responsiveness to tamoxifen in cases with a positive hormone receptor status. Our results highlight the biological and clinical relevance of IGF1R in early breast carcinoma subtypes, and provide knowledge to assist in treatment decision.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / mortality
  • Chi-Square Distribution
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • In Situ Hybridization
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers, Tumor
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2
  • Receptor, IGF Type 1