We investigated the
epidermal growth factor receptor (EGFR) status in early stage
lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell
lung cancers,
adenocarcinomas (AC),
squamous cell carcinomas (SqCC), and
large cell carcinomas were analyzed using a combination of techniques for the analysis of
protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with
antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific
antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and
squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific
antibodies. High expression of total EGFR
protein was correlated to high gene copy numbers but did not reflect the mutational status of the
tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific
antibodies, and we also raise some other issues regarding the use of the mutation-specific
antibodies, for example concerning heterogeneous expression of the mutated
protein, optimal antibody dilution, and discrepancies between staining results and PCR.