Combined EGFR/ALK Expression Analysis in Laryngeal Squamous Cell Carcinoma

Abstract

Background/Aim: Epidermal growth factor receptor (EGFR) acts as an oncogene in malignancies. Our aim was to examine the role of combined EGFR/ anaplastic lymphoma kinase (ALK) expression as molecular markers in laryngeal squamous cell carcinoma (LSCC) patients. Materials and Methods: Fifty (n=50) tissue sections derived from twenty-five (n=25) primary LSCCs were analyzed by immunohistochemistry (IHC). Results: EGFR overexpression was observed in 17/25 (68%) cases. Concerning ALK, 23/25 (92%) demonstrated low expression. EGFR expression was associated with grade (p=0.049), whereas ALK expression was correlated with stage (p=0.048). ALK overexpression was detected at advanced-stage EGFR-positive cases. A biphasic EGFR protein expression pattern was observed in five (n=5) LSCC cases, whereas ALK expression was stable in all cases. Conclusion: EGFR overexpression is frequently observed in LSCC combined with low ALK expression. LSCC patients with EGFR/ALK protein overexpression should be eligible for targeted therapeutic strategies. Molecular analyses in solid malignancies-including laryngeal squamous cell carcinomas (LSCC)-have shown that upregulation of specific growth factor receptors critically destabilize the cell micro-environment inducing signal transduction from the membrane to the nucleus (1). Among these molecules, epidermal growth factor receptor (EGFR) plays a crucial role in this process. The EGFR (other names include: ERBB, ERBB1, or HER1) gene is located on the short (p) arm of chromosome 7 at position 12 (cytogenetic chr band 7p12.1) (2). The protein encoded by the corresponding gene acts as a transmembrane glycoprotein. It is a member of the verb -b2 erythroblastic leukemia viral oncogene (ErbB)/human epidermal receptor (HER) family of receptor tyrosine kinases, that includes also other three cell membrane receptor tyrosine kinases: HER2/c-neu (ERBB2), HER3 (ERBB3) and HER4 (ERBB4). Three main EGFR depended pathways have been already identified including the PI3K-AKT-PTEN-mTOR, the RAS-(B) RAF-MEK-ERK/MAPK and also the IL6-JAK1/2-STAT3 (3). Concerning LSCC, a subset of patients exhibits EGFR activating mutations (approximately 10-30%) and also gene amplification (approximately 10-35%) leading to protein overexpression (4, 5). Similarly, deregulation of anaplastic lymphoma kinase (ALK) seems to be a novel marker in handling LSCC patients with EGFR aberrant expression. ALK gene is located at chromosome 2 (2p23 band) encoding a protein which acts as a transmembrane receptor tyrosine kinase 815 This article is freely accessible online.

Impact of K-Ras Over-expression in Laryngeal Squamous Cell Carcinoma

“…Another study group co-analyzing EGFR and KRAS mutations in Greek NSCLC patients detected a low-level mutational status, but KRAS mutations should be considered an independent prognostic factor that negatively affects prognosis in these patients (21). Similarly, another study showed that high co-expression of EGFR and another important molecule (anaplastic lymphoma kinase (-ALK) are associated with an aggressive biological behaviour (advanced stage/grade) in LSCCs (22). Concerning novel micro-genetic markers such as micro-RNAs, a study group showed that a specific variant allele in the KRAS 3' untranslated region involving the let-7 miRNA complementary site (KRAS-LCS6) is associated with aberrant KRAS expression.…”

ALK Protein Expression Patterns in Squamous Cell Carcinoma of the Oral Cavity

“…Similarly, in a previous study, we showed that EGFR overexpression is frequently detected combined with minimal ALK expression. Patients with OSCC demonstrating EGFR/ALK protein overexpression fulfill the genetic criteria for targeted therapeutic strategies (20).…”

C-Fos Digital Expression Analysis in Human PapillomavirusRelated Oral Squamous Cell Carcinoma

“…Concerning c-fos protein expression evaluation, we implemented a DIA protocol that provides an objective, accurate and fast mean for measuring the immunostaining intensity levels. According to our published experience in a variety of biomarkers, DIA is a useful tool for research and diagnostic reasons -under specific terms-enhancing the innovative evidencebased medicine [18][19][20][21][22].…”