Epidermal Growth Factor Receptor and K-RAS status in two cohorts of squamous cell carcinomas

Abstract

BackgroundWith the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. The aim of this study was to analyse EGFR expression, EGFR gene copy number and EGFR and K-RAS mutations in two cohorts of squamous cell carcinomas, specifically anal canal and tonsil carcinomas.MethodsFormalin fixed, paraffin-embedded tissues from anal and tonsil carcinoma were used. EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. For the K-RAS gene, PCR was performed using exon 2 specific primers.ResultsEGFR immunoreactivity was present in 36/43 (83.7%) of anal canal and in 20/24 (83.3%) of tonsil squamous cell carcinomas. EGFR amplification was absent in anal canal tumours (0/23), but could be identified in 4 of 24 tonsil tumours.From 38 anal canal specimens, 26 specimens were successfully analysed for exon 18, 30 for exon 19, 34 for exon 20 and 30 for exon 21. No EGFR mutations were found in the investigated samples. Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. From 24 tonsil specimens, 22 were successfully analysed for exon 18 and all 24 specimens for exon 19, 20 and 21. No EGFR mutations were found. Twenty-two samples were sequenced for K-RAS exon 2 and one mutation c.53C > A was identified.ConclusionEGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. EGFR amplification was seen in tonsil but not in anal canal carcinomas. In our investigated panel, only one mutation in the K-RAS gene of a tonsil squamous cell carcinoma was identified. This indicates that EGFR and K-RAS mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in anal canal and tonsil squamous cell carcinoma.

The prognostic significance of epidermal growth factor receptor expression in patients with anal carcinoma

“…He observed increased EGFR expression in 21 patients in total, which presents 55% [21]. Several other studies were then published, finding EGFR expression between 58% -100% [22][23][24][25]. In our study we observed EGFR expression in one half of the patients.…”

“…Van Damme described EGFR expression 1+ in 7 patients, EGFR expression 2+ in 12 patients, and EGFR expression 3+ in 17 patients. In total, he observed EGFR expression in 83.7% patients [23]. We observed no EGFR Potential subjective influence on EGFR expression evaluation using immunohistochemistry should also be emphasized.…”

Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers

“…This lack of understanding is the primary factor hindering the effective use of these agents. In HNSCC, classical driver mutations of the pathway, such as PTEN and EGFR mutations, are rare, as are mutations in ERBB2-4 and members of the RAS pathway (23)(24)(25)(26)(27). To resolve this question, we undertook a detailed genomic dissection of the EGFR/PI3K pathway in oral cancer, the most common subsite of HNSCC.…”

Common Docking Domain Mutation E322K of the ERK2 Gene is Infrequent in Oral Squamous Cell Carcinomas

“…Mutations in EGFR (Hsieh et al, 2011;Szabó et al, 2011;Van Damme et al, 2010) and Ras (Hsieh et al, 2011;Murugan et al, 2012) and over expression of EGFR (Laimer et al, 2007), adaptor protein SHC (Plyte et al, 2000), G protein Rap (Mitra et al, 2003), and guanine nucleotide exchange factor SOS (Severino et al, 2008) have been reported in OSCC lesions. While none of the studies had investigated on the activating mutations in ERK2 gene, we observed and reported a single point mutation in the common docking domain of ERK2 (E322K) in an oral squamous cell carcinoma cell line in our previous study (Arvind et al, 2005).…”