Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung

Abstract

Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers exist for either selecting appropriate candidates or for predicting clinical recurrence. The purpose of the present study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGFR1) in lung adenocarcinoma. Tumor specimens were collected from 182 patients who underwent a complete resection for adenocarcinoma of the lung. The expression of IGFR1 was evaluated by immunohistochemistry. The genetic status of the epidermal growth factor receptor (EGFR) and K-ras genes was also investigated by PCR-based analyses. Immunohistochemistry and real-time PCR assays were used to evaluate the MET gene association with tyrosine phosphorylation and hepatocyte growth factor (HGF) status, and amplification, respectively. Positive expression of IGFR1 was detected in 43 (23.6%) of the 182 cases. A positive IGFR1 expression was also identified in 12 (42.9%) and 31 (20.1%) of the patients with and without recurrence, respectively (p=0.009). Logistic regression models indicated that positive staining for IGFR1 expression was an independent factor associated with tumor recurrence. IGFR1 expression was associated with a poorer disease-free survival (DFS). Multivariate analysis demonstrated positive IGFR1 expression to be independently associated with an increased risk for poor DFS. The tumors appearing positive for IGFR1 were more frequent among those with K-ras mutations when compared with the wild-type group. IGFR1 expression was associated with reduced DFS correlating with postoperative recurrence. Therefore, the expression status of IGFR1 can be a candidate surrogate marker to select patients who may benefit from adjuvant chemotherapy.

Figure 1.

Representative IHC staining. (A) Positive staining for IGFR1 with brown-stained membrane is viewed at low power (original magnification, x100). (B) Negative staining for IGFR1 is shown.

Figure 2.

Kaplan-Meier DFS curves stratified by IGFR1 expression. The heavy and narrow lines indicate positive and negative expression of IGFR1, respectively.