Signification and expression of pyruvate kinase M2, Akt and hypoxia inducible factor-1 in choroidal melanoma

Background: Researches showed that tumor pyruvate kinase M2 (M2-PK) is a novel marker of multiple tumors. Investigating the influence of M2-PK expression as well as hypoxia inducible factor-1 (HIF-1) and PI3K/Akt pathway on the biological behaviour of choroidal melanoma (CM) is of an important significance. Objective: The purpose of this study was to investigate the expression of M2-PK, Akt and HIF-1 in CM and discuss their effects in the development of CM. Methods: Thirty CM samples and 30 nevus samples were collected in Affiliated Hospital of Qingdao University Medical College. The percentages of M2-PK, Akt and HIF-1 expression in CM and nevus were detected by immunohistochemistry, and their association with clinicopathological parameters were statistically analyzed. The differences of the expressions of M2-PK, Akt and HIF-1 were evaluated by Chi-square test, and the correlations between M2-PK and Akt or HIF-1 were analyzed by correlation analysis of paired data. Results: The percentages of positive expression of M2-PK and Akt in CM were 73% (22/30) and 80% (24/30), respectively, and those in nevus were 40% (12/30) and 47% (14/30) respectively, showing significant differences between the two types of tumors (χ² = 6.787, P = 0.009; χ² =7.177, P = 0.007). An insignificant rate was found in HIF-1 expression in CM between the two types of tumors (70% versus 50%, χ² = 2.500, P = 0.114). The positive expressing percentage of M2-PK was 57% (8/14) in spindle cell type CM, 87% (7/8) in epithelioid cell type CM and 87% (7/8) in mixed cell type CM, with significant difference among them (χ² = 3.617, P = 0.172). M2-PK was positively expressed in 44% (4/9) of small CM, 85% (11/13) of moderate CM and 87% (7/8) of big CM, presenting a significant difference among them (χ² = 5.508, P = 0.064). An increasingly expressing percentage of M2-PK was seen in sclera invasive CM (94%) compared with sclera uninvasive CM (50%) (χ² = 7.308, P = 0.007). The correlations were seen in the expressing percentage between M2-PK and Akt (χ² = 12.315, P = 0.000) as well as between M2-PK and HIF-1 (χ² = 17.175, P = 0.000) or between Akt and HIF-1 (χ² = 10.159, P = 0.001). Conclusions: The expression of M2-PK upregulates in CM, indicating that M2-PK plays an important role in the survival, development, invasion and metastasis of CM probably by PI3K/Akt-HIF-1 pathway.