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Prognostic impact of epidermal growth factor receptor (EGFR) mutations in lung cancer

Thesis

Last updated: 06 Feb 2023

Subjects

-

Tags

Clinical & Chemical Pathology

Advisors

Gaafar, Taghrid M. , O'Brien, Mary , Nassef, Ayat-Allah A.

Authors

Abdel-Raouf, Fattma Hasan

Accessioned

2017-07-12 06:41:21

Available

2017-07-12 06:41:21

type

M.D. Thesis

Abstract

Background and Aim: Molecular biomarkers have been investigated in non-small cell lung cancer (NSCLC) and targeted treatments in advanced disease are established. However, there are no established targeted therapies at the moment for small cell lung cancer (SCLC). The aim of this study was to examine for the presence of known molecular targets in patients with SCLC and their prognostic effect. Patients and Methods: A panel of histopathologically proven FFPE specimens of SCLC were analysed for EGFR, KRAS, NRAS, BRAF mutations, ALK gene rearrangements and MET amplification. EGFR and KRAS testing were done using real time-polymerase chain reaction (RT-PCR cobas®), BRAF and NRAS using Multiplex PCR and capillary electrophoresis-single strand conformation analysis (CE-SSCA) and ALK and MET using fluorescent in situ hybridization (FISH). Any positive results were repeated for confirmation. Any inconsistent results were sequenced using the direct Sanger sequencing. Results: Sixty samples were suitable for molecular testing, with 25 successfully examined for all 6 markers. No mutations in EGFR were detected in the 31 cases suitable for analysis. KRAS and NRAS mutational analysis was successful in 35 and37 cases respectively; all of which were wild type. Fifty eight cases were assessed for ALK gene rearrangements and 42 cases for MET gene amplifications; no rearrangements or amplifications were detected. Forty seven samples were successfully analysed for BRAF mutations, with one V600E mutation (2.1% of cases). This patient was a 55 years old Caucasian male smoker diagnosed with lung cancer, treated with lobectomy and his post-lobectomy pathology revealed SCLC with squamoid and glandular features (positive BRAF mutation and negative for the rest of the markers). Conclusion: EGFR, KRAS, NRAS, ALK and MET were not detected in the examined panel of SCLC patients. One BRAF mutation was identified in a patient with a diagnosis of SCLC with mixed cellularity; the mutation was probably in the squamoid component. These biomarkers do not need to be further explored in SCLC.

DOI

http://dx.doi.org/10.21473/iknito-space/36554

Details

Type

Thesis

Created At

28 Jan 2023