Expression of FoxM1 and the EMT-associated protein E-cadherin in gastric cancer and its clinical significance

Abstract

The aim of the present study was to investigate the expression of forkhead box M1 (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any correlation between FoxM1, E-cadherin and clinicopathological parameters. The association between FoxM1 and E-cadherin in the development and progression of gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in gastric cancer and adjacent normal tissue on tissue microarray was detected using immunohistochemistry. The clinicopathological significance of FoxM1 and E-cadherin in gastric cancer was explored, and the association between FoxM1 and E-cadherin was further examined using statistical techniques. In gastric cancer tissues, the expression of FoxM1 and E-cadherin was strongly positive, but it was weak in normal gastric mucosa. Overexpression of FoxM1 was evident in gastric cancer, and was associated with poor tumor differentiation (P<0.05), advanced tumor state (P<0.05) and lymph node (or distant) metastasis (P<0.05), whereas E-cadherin had the opposite effects. Furthermore, the correlation between FoxM1 and E-cadherin expression in gastric cancer tissue was negative. In conclusion, the high FoxM1 expression and low E-cadherin expression in gastric cancer tissue suggests that these proteins play a critical role in the development and progression of gastric cancer.

Keywords: E-cadherin; FoxM1; gastric cancer.

Figure 1.

FoxM1 expression in samples of gastric cancer and its association with pathological features. (A) FoxM1 expression was detected by immunohistochemical analysis of tissue microarrays. Representative images of FoxM1 expression in normal gastric mucosa and gastric cancer tissue are shown (magnification, ×100, and ×200 for the inserts). The staining of FoxM1 in the normal gastric mucosal cells was negative, whereas the staining of FoxM1 in gastric cancer tissue cells was strongly positive. (B) FoxM1 expression was positively correlated with tumor stage (P<0.001 for stages I and II vs. stages III and IV). Representative images of stage I (weakly positive) and III (strongly positive) tumors are shown (magnification, ×200). (C) FoxM1 expression was positively correlated with tumor differentiation (P=0.002 for grades I and II vs. grade III). Representative images of grade II and III tumors are shown (magnification, ×200). (D) FoxM1 expression was positively correlated with lymph node (or distant) metastasis (P<0.001 for non-metastasis group vs. metastasis group). Representative images of gastric cancer with or without metastasis are shown (magnification, ×200). FOXM1, forkhead box M1.

Figure 2.

E-cadherin expression in samples of gastric cancer and its association with pathological features. (A) E-cadherin expression was detected by immunohistochemical analysis of tissue microarrays. Representative images of E-cadherin expression in normal gastric mucosa and gastric cancer tissue are shown (magnification, ×100, and ×200 for the inserts). The staining of E-cadherin in normal gastric mucosa cells was strongly positive, whereas in gastric cancer tissue cells, it was weakly positive or negative. (B) E-cadherin expression was negatively correlated with tumor stage (P=0.029 for stages I and II vs. stages III and IV). Representative images of stage I and III tumors are shown (magnification, ×200). (C) E-cadherin expression was negatively correlated with tumor differentiation (P=0.050 for grades I and II vs. grade III). Representative images of grade II (strongly positive) and III (weakly positive) tumors are shown (magnification, ×200). (D) E-cadherin expression was negatively correlated with lymph node (or distant) metastasis (P=0.037 for non-metastasis group vs. metastasis group). Representative images of gastric cancer with or without metastasis are shown (magnification, ×200).

Figure 3.

Co-expression of FoxM1 and E-cadherin expression in gastric cancer. (A) Immunohistochemical staining was performed with antibodies against FoxM1 and E-cadherin in gastric cancer tissue. Representative images of strongly-positive FoxM1 and negative E-cadherin staining are shown (magnification, ×100, and ×200 for the inserts). (B) Representative images of strong/moderate FoxM1 and moderate E-cadherin staining in gastric cancer sections are shown (magnification, ×100, and ×200). (C) A direct correlation between FoxM1 and E-cadherin expression in gastric cancer tissue was identified (n=70; Spearmans rank correlation test, r=−0.255; P=0.035). Of note, certain dots on the graph represent >1 sample (overlapped scores). (D) Summary of the expression of FoxM1 and E-cadherin in 70 gastric cancer samples. FoxM1, forkhead box M1.