Objective:To study the protein and mRNA expressions of von Hipple-Lintau gene protein(VHL)，hypoxia inducible factor-1 alpha (HIF-1α) and MV counts in the benign and malignant lesions of stomach and their clinicopathological significances.
Methods:EnVisonTM immunohistochemistry was used for detecting the expression of VHL and HIF-1α and MV counts and in situ hybridization was used for assaying the expression levels of VHLmRNA and HIF-1amRNA in conventional paraffin-embedded sections from the specimens of gastric cancer (n=49), peritumoral tissues(n=20), lymph metastassis (n=36), and different types of benign lesions(n=80).
Results:The positive expression rate of VHL protein and mRNA was significantly lower in gastric cancer, than that in peritumoral tissues and different types of benign lesions (P<0.05 or P<0.01),but experssion of HIF-1α protein and mRNA was the opposite (P<0.05 or P<0.01）.The means of MV counts were significantly higher in gastric cancer than those in peritumoral tissues and different types of benign lesions(P<0.01).The negative cases of VHL protein and mRNA expression and/or positive cases of HIF-1α protein and mRNA expression in benign lesions and peritumoral tissues showed mild-to severely-atypical hyperplasia of muscous epithelia. No difference was found between the primary foci and metastatic foci of lymph node on the expressive levels of VHL HIF-1α protein and mRNA and MV counts (P>0.05).In gastric cancer the positive rates of HIF-1α protein and mRNA and the means MV counts were significantly lower in histologic grade Ⅱ,infiltrating depth T1+T2,no-metastasis of lymph node or distant organs than those in histologic grade Ⅲ+Ⅳ, infiltrating depth T3+T4, metastasis of lymph mode or distant organ, (P<0.05 or P<0.01）, but the positive rate of VHL protein and mRNA was opposite to that of HIF-1α protein and mRNA (P<0.05). A high unconsistence was found between the expressive levels of VHL protein and HIF-1α protein and mRNA in gastric cancer tissues (χVHL=14.66，P<0.01，χVHLmRNA=6.74, P<0.05). The means of MV counts were significantly higher in the negative cases of VHL protein and mRNA or the positive ones of HIF-1α protein and mRNA than those in the positive cases of VHL protein and mRNA or the negative ones of HIF-1α protein and mRNA in gastric cancer tissues (P<0.01).
Conclusions:The expression levels of VHL and HIF-1α and mRNA might be important biological markers for reflecting the carcinogenesis, progression, biological behaviors and prognosis of gastric cancer. They might exert a negative regulated effect on the carcinogenesis and progression of gastric cancer.VHL might have inhibitive effects and HIF-1α and might have promotive effects on angiogenesis of gastric cancer.