Epidermal Growth Factor Receptor (EGFR) and Keratin 5 (K5): Versatile Keyplayers Defining Prognostic and Therapeutic Sub-classes of Head and Neck Squamous Cell Carcinomas.

ABSTRACT

Molecular classifications of several malignancies are already accepted and applied in clinical practice. For head and neck squamous cell carcinomas (HNSCCs) there exist few and controversial data regarding their stratification on distinct groups or sub-groups and thus, none of them are validated as useful tools for diagnosis and therapy. Starting from the highly expressed markers in HNSCC (epidermal growth factor receptor, keratin 5 and E cadherin) we proposed to identify distinct HNSCC sub-groups with a potential impact on prognosis and therapy. Complex analysis of immunohistochemical expression for six surrogate markers (EGFR, p53, Bcl2, CD117, keratin 5 and E-cadherin) defined three distinct sub-classes amongst EGFR-positive cases, based on the association and differential expression of p53 and Bcl2 (EGFR(+)/p53(-)/bcl2(-), EGFR(+)/p53(+)/bcl2(-) and EGFR(+)/p53(+)/bcl2(+)). Amongst them, only the EGFR(+)/p53+/bcl2(-) sub-class showed significant correlations with grade and TNM parameters. Keratin 5-positive cases were grouped in a special "basal like" group with a particular sub-class rich in CD117(+)/p63(+) cells also highly expressing EGFR. Presence of K5(+)/CD117(+)/p63(+) cells was correlated with all TNM staging parameters defining a particular sub-class with high aggressiveness and particular behavior. Our data sustain EGFR as the key player in the pathogenesis of HNSCCs, but its diagnostic value may be improved by association with other prognostic or therapeutic markers. We herein defined two distinct HNSCCs groups (EGFR(+) and K5(+)) with several sub-classes, identifiable by the additional assessment of p53, Bcl2 and CD117.