Skp2 and salivary cancer

• Published in: Cancer biology & therapy 2009-01, Vol.8 (2), p.153-158
• Main Authors: Ben-Izhak, Ofer, Akrish, Sharon, Gan, Shlomit, Nagler, Rafael M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Binding; Biology; Biomarkers, Tumor - metabolism; Bioscience; Calcium; Cancer; Carcinoma - classification; Carcinoma - genetics; Carcinoma - pathology; Cell; Cycle; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Female; Gene Expression Regulation, Neoplastic; Glucuronidase - metabolism; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Kaplan-Meier Estimate; Landes; Male; Middle Aged; Organogenesis; Probability; Prognosis; Proteins; S-Phase Kinase-Associated Proteins - metabolism; Salivary Gland Neoplasms - genetics; Salivary Gland Neoplasms - mortality; Salivary Gland Neoplasms - pathology; Survival Analysis; Time Factors; Tumor Suppressor Protein p53 - metabolism; Young Adult
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.8.2.7114

Salivary malignancies are rare, heterogeneous, unpredictable in clinical behavior and seldom studied. Skp2 expression was examined in salivary malignancies (n=75) for a prolonged period (20 years). In 40/75 (53%) cases Skp2 expression rate (staining level) was ≤4% while in the remainder (47%) it was >4%. Correlation between enhanced Skp2 and enhanced p53 staining levels was significant (p=0.042), as were correlation rates between enhanced Skp2 and reduced p27 staining levels (p=0.01) and enhanced Skp2 and enhanced TUNEL staining levels (p=0.008). Survival probability rates dropped when Skp2 expression increased. Median patient survival for reduced-stained-tumor patients (≤4%) was 143 months and significantly lower, 49 months (p=0.016), for enhanced-stained-tumor patients (>4%). Survival probability at 5 years was 82% for the former group (≤4%) and 47% for the latter (>4%). At 20 years, survival dropped to 35% and 18% respectively (p=0.016). More extensive and aggressive therapy did not reduce mortality in patients with enhanced Skp2-expressing tumors. Significant correlations between poor survival and significantly altered expression rates of Skp2, p27, p53, TUNEL and heparanase in salivary malignancies, suggest a biological role in salivary cancer pathogenesis for these 5 markers. The findings may be used for prognostic and follow-up purposes.