title: Skp2 and salivary cancer.
abstract: 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 < or =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 (< or =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 (< or =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.
authors.affiliation: Department of Pathology, Rambam Medical Center, Haifa, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Ben-Izhak
authors.forename: Sharon
authors.initials: S
authors.lastname: Akrish
authors.forename: Shlomit
authors.initials: S
authors.lastname: Gan
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000145:classification / Q000235:genetics / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult; D000099175:Heparanase
chemical_list: D014408:Biomarkers, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005966:Glucuronidase; D044786:S-Phase Kinase-Associated Proteins; D016159:Tumor Suppressor Protein p53; D000099175:Heparanase