Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma

Abstract

Abstract. Epidermal growth factor receptor (EGFR) gene mutations have been reported to be clinically significant in non-small cell lung cancer (NSCLC). However, because most previous studies focused only on adenocarcinomas, EGFR mutations in other histotypes are poorly investigated. We evaluated the frequency of EGFR gene mutations in squamous cell carcinoma (SCC) and its clinicopathological features. In total, 89 frozen tumor specimens that had been first diagnosed as SCCs, were examined for EGFR mutations in exons 19 and 21 using direct sequencing, PNA-enriched sequencing and SmartAmp2. Additionally, pathological investigation, including immunostaining for p63 and TTF-1, alcian blue staining and EGFR mutation-specific immunohistochemistry in mutation-positive samples was also performed. The frequency of EGFR mutations was 5.6% (5/89); all mutations were deletions in EGFR exon 19. Immunohistological investigation of these samples revealed that two of five were positive for p63 and TTF-1 staining, and showed production of mucin, as evidenced by alcian blue staining. Consequently, three of the samples were considered to be true SCC at final pathological diagnosis, while the remaining two samples were revised to adenosquamous carcinoma and adenocarcinoma. The final frequency of the EGFR mutations in true SCC was 3.4% (3/87). In conclusion, EGFR mutations were found in a small, but significant, number of SCC tumor samples and thus EGFR mutational analysis was useful in the accurate diagnosis of SCC. Our data demonstrate that EGFR mutational analysis should be performed not only in adenocarcinoma, but also in SCC to allow accurate diagnosis and treatment.

Clinical and genetic features of lung squamous cell cancer in never-smokers

“…Furthermore, our comparison the clinicopathological characteristics of SQCCs and the profiles of major known oncogenic mutations revealed that SQCCs arising in never-smokers distinctly differ from those in the more common smoking-related SQCCs. Oncogenic mutations, especially EGFR mutations, occurred considerably more frequently in the never-smokers, which is consistent with findings from an earlier study [18]. …”

“…For lung ADCs, driver mutations to EGFR , KRAS , HER2 , BRAF and AKT1 have been well reported [6, 13–15], and considerable progress has been made in their treatment [16]. However, whether lung SQCCs harbor these known driver mutations remains controversial [17, 18]. Lung SQCCs are strongly associated with tobacco exposure and are characterized by a high mutational burden with a mean somatic mutation rate of 8.1 mutations per megabase [19].…”

Genetic alteration profiling of patients with resected squamous cell lung carcinomas

“…Recently, Rekhtman et al screened 95 biomarker-verified SqCLC and reported that EGFR/KRAS mutations do not occur in pure SqCLC, occasional detection of these mutations in samples diagnosed as “SqCLC” is due to the diagnosis of adenosquamous carcinoma (AD-SQC) and adenocarcinoma [18]. However, another similar study by Miyamae et al revealed that EGFR mutations were present in 3.4% of 87 validated SqCLC specimens [20]. In our study, we found that the frequencies of EGFR and KRAS mutation were 3.2% and 4.5%, respectively, which were comparable with the previous reports of 3.4% [20] and 4% [22], respectively.…”

Q787Q EGFR Polymorphism as a Prognostic Factor for Lung Squamous Cell Carcinoma

“…The EGFR mutation rate is about 50% among nonselected lung adenocarcinoma cases in East Asian populations [24], and an approximately 60% response rate was identified when they were treated with an EGFR-TKI [5,6,7,25,26,27]. On the other hand, only an approximately 5% EGFR mutation rate was detected in lung squamous cell carcinoma [28,29]. Furthermore, the median progression-free survival among patients with lung squamous cell carcinoma who showed a partial response to EGFR-TKIs seemed to be shorter than that commonly observed with lung adenocarcinoma (4-5 vs. 9-10 months) [30].…”