VEGF/VEGFR2 Axis in Periodontal Disease Progression and Angiogenesis: Basic Approach for a New Therapeutic Strategy.

Periodontal lesions are associated with activation of pathological angiogenesis and a high number of newly-formed blood vessels. Most angiogenic growth factors have been studied in the crevicular fluid or serum, but tissue correlations with vascular density or endothelial proliferation, are very rare, even inexistent. We assessed the VEGF/VEGFR2 axis expression in a multimodal fashion, in both epithelial and stromal compartments, with emphasis to endothelial proliferation and severity of periodontal lesions. Compared to normal gingiva, negative for VEGF/VEGFR2, periodontal lesions had a progressive increase for these markers from low to severe periodontal lesions. The transition from low to moderate periodontal lesions represents the milestone in disease progression and implies an active angiogenesis based on the highest angiogenic parameter variability observed for these lesions. Epithelial vascularization was firstly observed in moderate periodontal lesions and persists during severe periodontal disease. All the parameters used to quantify angiogenesis in periodontal lesions, were significantly increased in severe periodontal lesions dependent on VEGF expression in both the epithelial and stromal compartment. Our results support the use of anti-VEGF/VEGFR2-targeted therapy as adjuvant treatment for severe periodontal lesions.

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

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.