EGFR, Bcl-2, p53, and cox-2 are associated with tumor stage, response to treatment, and survival in Korean nasopharyngeal carcinomas

Proc Amer Assoc Cancer Res, Volume 47, 2006 4481 Backgound: Nasopharyngeal cancer (NPC) is a unique tumor displaying quite different pathogenesis, biological behavior, and treatment strategies compared to head and neck cancer occurring other sites. According to WHO classification, NPC is divided into three histological categories including keratinizing squamous cell carcinoma, non-keratinizing carcinoma, and undifferentiating carcinoma. Purpose: The aim of this study was to investigate an association between the expression of EGFR, Bcl-2, p53, and cox-2 and clinical parameters of NPC. In addition, we wanted to identify whether they could be utilized as a biomarker. Method: Seventy-five locoregionally advanced NPC patients, pathologically diagnosed at Kangnam St. Mary’s Hospital and St Mary’s Hospital from 1992 to 2003 and treated with concurrent chemo-radiotherapy (CCRT) as induction treatment, were enrolled into our study. Using immunohistochemistry, the expression of EGFR, Bcl-2, p53, and cox-2 were evaluated on paraffin-embedded tumor tissues. Their labeling indices were counted as the percentage of nuclear staining cells and were scored semi-quantitatively. We statistically analyzed a relationship between their expres sion levels of EGFR, Bcl-2, p53, cox-2 and WHO classification, TNM stage, tumor response to CCRT, disease free survival (DFS), and overall survival (OS). Results: EGFR positive rate was 87.5% (66/75) and grading of its expression was significantly correlated with TNM stage (P=0.05). Bcl-2, showing 66.7% of positive rate (51/75) was correlated only with WHO classification. The expression of p53 (83.3%) had significant correlation with OS (P=0.043), but no correlations with staging and tumor response were found. Meanwhile, cox-2 immunoreactivity, detected in 86.1% (65/75), was significantly associated with lymph node response, DFS, and OS (P=0.049, 0.05, 0.0232, respectively). Conclusion: Taken together, it is considered that these four molecules might play important roles in carcinogenesis and tumor progression of NPC. Based on the interesting evidence that cox-2 expression was correlated with major clinical outcomes, the cox-2 inhibitors, known to potentiate the anti-tumor effects of chemotherapeutic drugs and radiation in preclinical studies, will be exploited in future clinical trials for treatment of NPCs.