Comparison of p53 and Epidermal Growth Factor Receptor Gene Status Between Primary Tumors and Lymph Node Metastases in Non-Small Cell Lung Cancers

To obtain insight into the cancer progression and metastatic process, we evaluate p53/epidermal growth factor receptor (EGFR) somatic aberrations in non-small-cell lung cancers to compare accumulated genetic alterations between primary tumors and lymph node metastases. A total of 56 primary lung cancers with corresponding lymph node metastases were identified to investigate somatic mutations and altered expressions of p53 and EGFR for clonality assessment. Genomic DNA was extracted from macrodissected cells of paraffin-embedded primary tumor and metastatic lymph node tissues. Overexpression and somatic mutations in exons of p53 (exons 5-8) and tyrosine kinase domain of EGFR (exons 18-21) were examined by immunohistochemical staining and DNA sequencing, respectively. p53 and EGFR mutation/overexpression status were different between primary tumors and lymph node metastases in 5.4/7.2% and 28.6/33.9%, respectively. In most cases, the p53 and EGFR mutations usually preceded lymph node metastasis, and these gene statuses in the primary cancer and their lymph node metastasis were concordant (92.9 and 69.6%, respectively), which further supported the hypothesis that when these p53 mutations occur before the establishment of lymph node metastasis, they subsequently persist in the metastatic nodes. The expressions of p53 and EGFR showed 7.1 and 33.9% discordance in that order. Our results reveal that p53 and EGFR mutations usually precede lymph node metastasis. The higher prevalence of EGFR heterogeneity existing in the primary tumor is not reflected in all lymph node metastasis and thus might have therapeutic implications when adjuvant therapy is considered.