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 ≤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 five 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 five markers. The findings may be used for prognostic and follow-up purposes.

S-phase kinase-associated protein 2 expression interference inhibits breast cancer cell proliferation

“…The SKP2 gene is a newly discovered cancer gene that is overexpressed in many cancers such as in gastric, lung, colon, prostate, ovarian, and laryngeal cancers, and in glioma (Lu et al, 2002;Takanami, 2005;Ben-Izhak et al, 2009;Shi et al, 2011;Wei et al, 2013). SKP2 is a member of the F-box protein family, which is necessary for DNA replication.…”

Immunohistochemical Analysis of Salivary Gland Tumors: Application for Surgical Pathology Practice

“…It was reported that, in small cell carcinomas, CK20-negative cases have a worse prognosis than the positive cases [51]. Bcl-2 (for adenoid cystic carcinoma) [37], E-cadherin (for adenoid cystic carcinoma) [26], p27 (for adenoid cystic carcinoma and mucoepidermoid carcinoma) [57, 73], MUC1 (for mucoepidermoid carcinoma) [28], glucose transporter type 1 (for salivary gland carcinoma) [46], heparanase [6], pRb2/p130 [61], vascular endothelial growth factor (for adenoid cystic carcinoma) [82], survivin [23, 72], RB1-inducible coiled-coil 1 [74], geminin [80], p63 (for adenoid cystic carcinoma) [60], Skp2 [7], EGFR [20, 21], c-kit [20], RUNX3 (for adenoid cystic carcinoma) [31], Cks1 [52], topoisomerase IIα [42], maspin [64], PI3K/AKT/mTOR [22, 75], and PTEN [21] were also reported to be significant IHC markers for evaluating the malignancy of the salivary gland carcinoma and for their prognostic estimation [65, 71]. …”

Possibility of the Use of Public Microarray Database for Identifying Significant Genes Associated with Oral Squamous Cell Carcinoma

“…STAT1 [6], SKP2 [7], IFI16 [8], RHEB [9], FIF44 [10], SOD2 [11, 12], and GREM1 [11] are related to OSCC. Table 6 [13-56] summarizes the previous studies that have published the relations of selected genes with cancer.…”

“…In salivary cancer, survival probability rates dropped when Skp2 was overexpressed [7]. Overexpression of Skp2 is associated with the reduction of p27 (KIP1) expression and may have a role in the progression of OSCC [25].…”

“…In previous studies, OSCC-related genes among the selected genes were STAT1 [14], SKP2 [7, 25], IFI16 [8], RHEB [9], IFI44 [64], SOD2 [10-12], and GREM1 [11]. The gene set, which has not been proven as OSCC-related genes until now, could be expected to be possibly proven as OSCC-related genes by biological evaluation.…”