c-MYC Protein Expression Patterns in Laryngeal-Hypopharyngeal Squamous Cell Carcinomas

Over activation of c-MYC oncogene (gene locus: 8q24.21) - predominantly due to the amplification of the gene - is a critical genetic imbalance involved in malignant transformation of normal epithelia. Our aim was to explore the differences in c-MYC protein expression in a series of laryngeal (LSCC) and hypopharyngeal squamous cell carcinomas (HPSCCs).

We retrospectively analyzed a set of sixty (n=60) paraffin embedded laryngeal-hypopharyngeal squamous cell carcinomas (L-PHSCC) tissue sections by immunocytochemistry (IHC) for the detection of c-MYC protein expression. A digital image analysis (DIA) algorithm was also performed for measuring objectively the corresponding immunostaining intensity levels of the examined protein. The correlation of c-MYC protein expression levels with various clinicopathological characteristics was assessed.

High and moderate staining intensity levels of c-MYC protein expression were identified in 46/60 (76.6%) of the examined cases (21/60 and 25/60, respectively), whereas the rest of them demonstrated low expression values (14/60, 23.4%). c-MYC expression was significantly correlated with the anatomic location of the malignancies (p=0.03), with the stage of the disease (p=0.004), as well as with the grade of differentiation (p=0.049). Interestingly, c-MYC diffuse nuclear/cytoplasmic expression was observed mainly in advanced-stage carcinomas.

c-MYC overexpression is a common feature in L-HPSCCs, mainly due to c-MYC oncogene overactivation. Increased levels of nuclear and diffuse cytoplasmic c-MYC protein are associated with aggressive phenotypes in patients with L-HPSCCs. Given the emerging interest in oncogene-targeted therapies in modern oncology, identifying patients with distinct c-MYC genetic, epigenetic, and proteomic signatures represents a promising strategy for personalized treatment approaches.