J Pathol Transl Med.  2015 Sep;49(5):382-388. 10.4132/jptm.2015.07.10.

Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma

Affiliations
  • 1Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. chungjh@snu.ac.kr
  • 2Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 3Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Abstract

BACKGROUND
Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC.
METHODS
IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance.
RESULTS
Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p = .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor (EGFR)-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p = .009).
CONCLUSIONS
Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR-mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.

Keyword

Carcinoma, non-small-cell lung; Insulin-like growth factor-1 receptor; Receptor, epidermal growth factor; Immunohistochemistry; Membranous expression

MeSH Terms

Adenocarcinoma*
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Cytoplasm
Disease-Free Survival
Epidermal Growth Factor*
Humans
Immunohistochemistry
Lung
Membranes
Prognosis*
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor*
Epidermal Growth Factor
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor

Figure

  • Fig. 1. Representative immunohistochemistry examples of membranous insulin-like growth factor-1 receptor (IGF1R) expression. IGF1R expression in non-neoplastic lung tissue (A), membranous IGF1R expression in squamous cell carcinoma (B), membranous IGF1R expression of adenocarcinoma (C).

  • Fig. 2. Kaplan-Meier survival analysis of progression-free survival and overall survival curves based on membranous insulin-like growth factor-1 receptor (IGF1R) expression. Membranous IGF1R expression had significantly better progression-free survival (A) and overall survival (B) in squamous cell carcinoma. Membranous IGF1R expression in epidermal growth factor receptor (EGFR)-mutant adenocarcinoma had significantly poor progression-free survival (C) and a trend toward poor overall survival (D).


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