High expression level of insulin-like growth factor I receptor is associated with regional lymph node metastasis

Abstract

4115 Background: Over-expression of the insulin-like growth factor I receptor (IGF-IR) has been found in many types of human cancers. In vivo, inhibition of the function of IGF-IR results in apoptosis and tumor growth attenuation, indicating that altered expression of IGF-IR may play an important role in human cancer. However, the role of IGF-IR in gastric cancer has not been explored. Methods: In this study, we determined the expression status of the IGF-IR in primary gastric cancer using immunohistochemistry. Results: In the 86 cases of resected gastric cancer examined, IGF-IR was over-expressed in 61.6% gastric tumor samples as compared to the adjacent cancer-free gastric mucosa (p=0.018). In patients with lymph node metastasis, high expression level of IGF-IR was detected in both the primary tumor site and metastatic tumor cells with lymph nodes (p=0.0102), implicating IGF-IR in the development of lymph node metastasis. It has been reported that the transcription factor Sp1 transactivates the IGF-IR promoter and regulates IGF-IR expression. We have previously showed that over-expression of Sp1 in gastric cancer associated with advanced stage and predicted poor survival. In the current study, the expression level of IGF-IR correlated with that of Sp1 (p=0.018). Further, the median survival for patients with low and high IGF-IR expression was 1242 days and 792 days, respectively. However, this survival difference was not statistically significant (p=0.16), indicating that a larger scale study is warranted to further determine the value of IGF-IR as a prognostic/survival marker. Conclusions: Taken together, our data suggest that alteration of IGF-IR expression is likely to play a significant role in the development and metastasis of gastric cancers. Although it is not an independent survival predictor, it is one of the essential down steam components of Sp1 that might affect patient outcome. No significant financial relationships to disclose.