Abstract A42: Characterization of EGFR and leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1–3) in esophageal carcinoma with emphasis on patient survival

Abstract

Abstract Background: Esophageal carcinoma is the seventh most common cause of cancer-related death in the Western world and the incidence is increasing. The signal transduction system of epidermal growth factor receptor (EGFR) is of major importance for tumor growth in several types of malignancies and EGFR-targeted therapy has been shown to able to regulate tumor growth. Leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1) is an endogenous negative regulator of EGFR signaling. The functions of LRIG2 and −3 are at present not known, however, it has been postulated that they might also be involved in the regulation of growth factor signaling and tumor growth. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG1–3 in esophageal carcinoma as well as the correlation between their expression levels and the chemosensitivity of esophageal carcinoma cell lines. Patients and Methods: A total of 86 patients diagnosed with esophageal carcinoma were included in the study and their tumors were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Further, a total of nine esophageal carcinoma cell lines were investigated for their expression of EGFR, LRIG1, −2 and −3 by quantitative RT-PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay. Results: Survival analysis using Kaplan-Meir analysis showed that the staining intensities of EGFR and LRIG2 were significantly associated with short survival (p=0.025 and p=0.03, respectively), whereas the extent of staining of LRIG1 was associated with long survival (p= 0.045). Chemosensitivity studies demonstrated a significant correlation between LRIG1 expression levels and sensitivity to cisplatin (r=−0.74), docetaxel (r=−0.69) and vinorelbine (r=−0.82) in the investigated esophageal carcinoma cell lines. Conclusion: In the present study, the expression of EGFR and LRIG2 correlated negatively, whereas LRIG1 correlated positively, with survival of the esophageal carcinoma patients. Furthermore, a correlation between LRIG1 expression and chemosensitivity was observed, indicating a possible role in chemoresistance. The functions of LRIG1 and −2 and their connection with EGFR warrants further investigation. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A42.