Expression, intracellular localization, and mutation of EGFR in conjunctival squamous cell carcinoma and the association with prognosis and treatment

Abstract

Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to determine molecular localization of epidermal growth factor receptor (EGFR) and the possibility of EGFR as a biomarker for the management of conjunctival SCC. Methods In this retrospective study, we performed immunohistochemistry to evaluate EGFR expression and localization in tumor cells, EGFR mutation-specific expression (E746-A750del and L858R), and human papillomavirus expression in a series of 29 conjunctival SCCs. Results All 29 tumors in our cohort were EGFR positive (100%). Twenty-one of 29 tumors (72%) showed focal EGFR staining, and seven (28%) showed diffuse EGFR staining. In addition, we calculated the percentages of the two most important mutations in EGFR (exon 19 746-A750del (8/29, 27.5%), exon 21 (L858R mutant (2/29, 6.8%)) in conjunctival SCCs. We observed that the translocation of EGFR from the membrane into the cytoplasm was related to clinical prognosis, as we detected correlations between EGFR cytoplasmic staining and final orbital exenteration and between decreased EGFR membrane staining and progression-free survival.

Expression of thrombospondin-1 in conjunctival squamous cell carcinoma is correlated to the Ki67 index and associated with progression-free survival

“…We also examined the molecular expression and intracellular localization of potential molecular target in conjunctival SCC in East Asian patients. [5] In 1978, thrombospondin-1 was initially reported to be a member of extracellular matrix (ECM) proteins that are widely present in normal human tissues and tumors. [6] Although it is well known that thrombospondin-1 suppresses angiogenesis, there are both reports that its expression is associated with tumor growth and the opposite in which it is negatively associated with tumor development, thereby indicating it could be a multifaceted molecular model.…”

Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review

“…Epidermal growth factor receptor (EGFR) has been reported to be overexpressed in cSCC. 5,6 Shepler et al 6 showed intense EGFR expression in both in-situ and invasive components of the cSCC. Later, Sakai et al 5 evaluated the molecular localization of the EGFR staining as a biomarker for the management of cSCC.…”

“…5,6 Shepler et al 6 showed intense EGFR expression in both in-situ and invasive components of the cSCC. Later, Sakai et al 5 evaluated the molecular localization of the EGFR staining as a biomarker for the management of cSCC. They observed a correlation between cytoplasmic EGFR staining and final orbital exenteration (hazard ratio: 4.2; p = 0.036) and between membrane EGFR staining and progression-free survival (hazard ratio: 0.23; p = 0.015).…”

Composites of Nucleic Acids and Boron Clusters (C2B10H12) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells

“…Epidermal growth factor receptor (EGFR) is one of the most promising molecular targets for anticancer therapy [ 1 ]. This receptor is a transmembrane protein located either on the cell surface or in a diffused form in the cytoplasm [ 2 ]. EGFR consists of three major functional domains: an extracellular ligand-binding domain, a hydrophobic transmembrane domain, and an intracellular enzymatic domain [ 3 , 4 , 5 , 6 ].…”