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

Abstract

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.

• Authors: Gloria Peiró, Encarna Adrover, Laura Sánchez-Tejada, Enrique Lerma, María Planelles, José Sánchez-Payá, Francisco I Aranda, Daniel Giner, Francisco J Gutiérrez-Aviñó
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 24 Issue 2 Pg. 201-8 (Feb 2011) ISSN: 1530-0285 [Electronic] United States
• PMID: 21057462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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