Clinicopathologic characteristics and prognostic significance of EGFR and p53 mutations in surgically resected lung adenocarcinomas ≤2 cm in maximal dimension.
OBJECTIVE
Small lung adenocarcinomas are detected more frequently than in the past. However, the clinicopathologic characteristics and prognostic significance of EGFR/p53 mutations in these tumors remains unclear.


METHODS
We evaluated the correlation of EGFR/p53 mutations with clinicopathologic characteristics and tumor relapse in 172 surgically resected lung adenocarcinomas ≤2 cm in maximal dimension. EGFR/p53 mutational analysis was performed on DNA extracted from paraffin-embedded tumors.


RESULTS
EGFR and p53 mutations were identified in 104 (60.5%) and 36 (20.9%) small adenocarcinomas, respectively. EGFR/p53 mutations were associated with tumor size >1 cm, whereas p53 mutations were frequently observed in moderately differentiated tumors. Disease-free survival analysis showed that p53 mutation, presence of visceral pleural surface invasion, elevated preoperative serum carcinoembryonic antigen, and moderate histologic differentiation were significantly correlated with tumor relapse in patients with stage I disease. The 5-year survival rate was higher in relapsed patients with EGFR-mutated tumors who were treated with tyrosine kinase inhibitor (TKI) than in those who were not treated with TKI.


CONCLUSIONS
p53 mutation was significantly correlated with tumor progression, and our findings may provide a rationale for the selective use of adjuvant chemotherapy in stage IB patients with p53 mutations. EGFR mutation was a predictor of EGFR TKI response in relapsed patients.
Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Mong-Wei
MW
Lin
Chen-Tu
CT
Wu
Jin-Yuan
JY
Shih
Yih-Leong
YL
Chang
Pan-Chyr
PC
Yang
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D018773:Genes, erbB-1; D016158:Genes, p53; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016019:Survival Analysis; D047368:Tumor Burden
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D005819:Genetic Markers; D011505:Protein-Tyrosine Kinases
epidermal growth factor receptor; lung adenocarcinoma; p53