[Correlation of Skp2 expression in gastric carcinoma to expression of P27 and PTEN].

BACKGROUND &

OBJECTIVE

S-phase kinase-associated protein 2 (Skp2) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of cyclin-dependent kinase inhibitor P27. Its overexpression has been involved in cell transformation and tumorigenesis. This study was to investigate the significance of Skp2 expression in human gastric carcinoma and its correlation to expression of both P27 and PTEN.

METHODS

The expression of Skp2 in 138 specimens of gastric cancer and their paired adjacent mucosa, 102 specimens of paired metastatic lymph nodes, 30 specimens of dysplasia, 30 specimens of intestinal metaplasia, 10 specimens of chronic superficial gastritis, and 5 specimens of normal gastric mucosa, and the expression of P27 and PTEN in 138 specimens of gastric cancer were detected by immunohistochemistry.

RESULTS

Skp2 labeling frequency was significantly higher in intestinal metaplasia [(12.68+/-0.86)%] and adjacent mucosa [(19.32+/-1.22)%] than in chronic superficial gastritis [(0.53+/-0.13)%] and normal gastric mucosa [(0.47+/-0.19)%] (P<0.001), but there was no difference between chronic superficial gastritis and normal gastric mucosa (P>0.05); Skp2 labeling frequency was significantly higher in dysplasia [(16.74+/-0.82)%] than in intestinal metaplasia (P<0.001), significantly higher in primary gastric carcinoma [(31.34+/-2.17)%] than in dysplasia and adjacent mucosa (P<0.001), and significantly higher in metastatic lymph node [(39.76+/-2.00)%] than in primary gastric carcinoma (P=0.037). Skp2 labeling frequency in gastric carcinoma was positively correlated with differentiation grade (rs=0.315, P<0.001), vessel invasion (rs=0.303, P<0.001), and lymph node metastasis (rs=0.254, P=0.001). Skp2 expression was negatively correlated with both P27 expression (rs=-0.451, P<0.001) and PTEN expression (rs=-0.480, P<0.001) in gastric carcinoma. P27 expression was positively correlated with PTEN expression in gastric carcinoma (rs=0.642, P<0.001).

CONCLUSION

Skp2 overexpression, which may lead to degradation of P27 and low expression of PTEN, may be a very important reason in carcinogenesis and progression of gastric carcinoma.