EGFR and p53 status of pulmonary pleomorphic carcinoma: Implications for EGFR tyrosine kinase inhibitors therapy of an aggressive lung malignancy
Journal
Annals of Surgical Oncology
Journal Volume
18
Journal Issue
10
Pages
2952-2960
Date Issued
2011
Author(s)
Abstract
Background: Pleomorphic carcinomas of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous components and are distinguished from other non-small-cell lung carcinomas by a more aggressive clinical course with early distant metastases and far worse survival. Epidermal growth factor receptor (EGFR) and p53 are common genes involved in the pathogenesis of non-small-cell lung carcinomas, but their roles in pleomorphic carcinomas are unclear. The potential clinical activity of EGFR-targeted therapy is also unknown. Methods: A total of 42 pleomorphic carcinomas were identified to investigate somatic mutations of EGFR and p53. Genomic DNA was extracted from microdissected cells of paraffin-embedded tumor tissues. Somatic mutations in EGFR (exons 18-21) and p53 (exons 5-8) were examined. Results: EGFR mutations were detected in 10 of 42 cases. Five of these patients had point mutations in exon 21 majorly with L858R; this mutation was found in both adenocarcinomatous and sarcomatous components in 1 case. The other 5 cases harbored 4 deletions and 1 mutation in exon 19. p53 mutations were found in 12 patients. Notably, identical mutation was observed in carcinomatous and sarcomatous components in 3 patients, and this finding strongly supported the theory of monoclonal histogenesis. Conclusions: The occurrence (23.8%) of EGFR mutations, including the exons 19 and 21 mutations observed frequently in our series, suggests that the patients with inoperable pleomorphic carcinomas are likely to benefit from treatment with EGFR tyrosine kinase inhibitors. ? 2011 Society of Surgical Oncology.
SDGs
Other Subjects
epidermal growth factor receptor; genomic DNA; paraffin; protein p53; protein tyrosine kinase inhibitor; adult; aged; article; cancer survival; clinical article; correlation analysis; exon; female; gene; gene amplification; gene deletion; histogenesis; human; human tissue; kras gene; lung carcinoma; lymph node metastasis; male; microdissection; point mutation; protein function; pulmonary pleomorphic carcinoma; sex difference; smoking habit; somatic mutation; tumor volume; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cohort Studies; DNA, Neoplasm; Female; Follow-Up Studies; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Mutation; Neoplasm Staging; Polymerase Chain Reaction; Prognosis; Proto-Oncogene Proteins; ras Proteins; Receptor, Epidermal Growth Factor; Small Cell Lung Carcinoma; Tumor Suppressor Protein p53
Type
journal article