Epidermal Growth Factor Receptor Copy Number Variations, but Not EGFR or KRAS Mutations, Are Frequent in Lung Squamous Cell Carcinomas
Ruth Roman, Natalia Rodon, Montse Verdu, Beatriz Garcia, Merce Pujol, Miquel Calvo, Xavier Puig. BIOPAT.Biopatologia Molecular, SL, Grup Assistencia, Barcelona, Spain; Hospital de Barcelona, SCIAS, Grup Assistencia, Barcelona, Spain; Histopat Laboratoris, Barcelona, Spain; Universitat de Barcelona, Barcelona, Spain
Background: Epidermal growth factor receptor (EGFR) mutations, and to a lesser extent EGFR copy number variations, have been correlated with response to EGFR tyrosine kinase inhibitors (TKIs). In contrast, KRAS mutations have been recently associated with resistance to TKIs. Most of these studies have been carried out on adecarcinomas (ACs) due to the association of this histologic type with the presence of alterations in the EGFR gene pathway. The aim of this study was the molecular characterization of a series of lung squamous cell carcinomas (SCCs) and the possible implications on TKIs therapy.
Design: A series of 47 surgically resected paraffin embedded SCCs were reviewed and their histological classification further confirmed by IHC (CK7, CK5/6, CK903, CK20, p63 and TTF1). The presence of EGFR and KRAS mutations was analyzed by direct sequencing and the incidence of EGFR copy number variations determined by fluorescent in situ hybridization (FISH). These results were then compared to those found in a series of 48 ACs and their statistical significance analyzed using Fisher's exact test.
Results: Despite there were no EGFR or KRAS mutations found in this series of SCCs, there was a high percentage of cases (55%) presenting EGFR copy number variations, which is not statistically different from that found in the series of ACs (p=0.14). These FISH positive SCCs included 6 cases with EGFR amplification and 20 cases with high polysomy.
Conclusions: Our results confirm the absence of EGFR and KRAS mutations in lung SCCs observed in other series. Nonetheless, the significant number of EGFR copy number variations observed, and the possible correlation with TKIs sensitivity cannot be overlooked and should be further analyzed. This study suggests that FISH may be an appropriate methodology to assess the EGFR status of SCCs.
|SCCs (n=47)||ACs (n=48)||P value|