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A4683 - High CD151 Expression in Non-Small Cell Lung Cancer (NSCLC) Patients Expressing Wildtype Epidermal Growth Factor Receptor (EGFR) Is Associated with Poorer Disease Outcome
Author Block: A. Wong1, M. Nga2, H. Wong3, R. Soo4, J. Tam5, Y. Lim2, J. Seet2, C. Chin1, T. Tran1; 1Physiology, National University of Singapore, Singapore, Singapore, 2Pathology, National University Singapore, Singapore, Singapore, 3Biostatistics, National University of Singapore, Singapore, Singapore, 4Hematology-Oncology, National University Hospital, Singapore, Singapore, 5Surgery, National University Singapore, Singapore, Singapore.
Rationale Epidermal growth factor receptor (EGFR)-targeted therapies are limited to advanced non-small cell lung cancer (NSCLC) patients who harbour EGFR mutation, leaving the remaining 70-90% wildtype EGFR patients with an urgently unmet medical need. The tetraspanin CD151 has been implicated in multiple cancer promoting processes such as tumour growth, angiogenesis and metastasis in several human malignancies including NSCLC. However, the significance of its expression and relationship with EGFR mutation status is not known. We investigated the association between CD151 expression levels with EGFR mutation status in NSCLC and determined the prognostic biomarker value of this relationship Methods Retrospective evaluation of 157 patients with NSCLC recruited from 1989-2011. Tissue microarray samples were stained and scored for CD151 expression levels by immunohistochemistry. CD151 high versus low expression differences were compared with patient clinicopathological parameters and clinical outcome. Results CD151 expression is strongly associated with EGFR mutation status (p=0.005) where the number of NSCLC cases with high CD151 expression was greater in wildtype EGFR (75%) compared with mutant EGFR group (54%). High CD151 expression was also associated with Chinese ethnicity (p=0.048), smoker status (p=0.022), and more advanced TNM (tumour, node. metastasis) stage (p=0.018), respectively. High CD151 expression alone, was shown to be an independent prognostic factor of disease-specific death (p=0.030). Importantly, following adjustment for confounding factors, higher cumulative incidence of death due to disease was observed in patients with both wildtype EGFR and high CD151 expression when compared against patients from the other subgroups (p=0.011). Given the association between CD151 expression and TNM stage, we investigated the impact of TNM early (Stage I and II) and advanced (Stage III and IV) stage on clinical outcome. There was no significant difference in cumulative incidence of time to disease death in the early TNM stage group, whereas in the advanced stage group, high CD151 with wildtype EGFR subgroup had significantly worse clinical outcome (p=0.002). Conclusion We show for the first time, that high CD151 expression is strongly associated with wildtype subgroup in NSCLC patients. Furthermore, high CD151 expression together with wildtype EGFR status results in significantly shorter survival time in NSCLC patients. This data supports further investigation and development of CD151 as a prognostic biomarker and/or therapeutic target for the management of NSCLC patients, especially those that express wildtype EGFR.