Expression And Clinical Significance Of PTEN, MMP-9, Survivin And Ki-67 In Retinoblastoma

Objective To investigate the expression of phosphatase and homology deleted on chromosome ten (PTEN), matrix metalloproteinase-9(MMP-9), Survivin and Ki-67 in retinoblastoma(RB) and their relationship with clinical-pathological parameters.Methods The expression of PTEN, MMP-9, Survivin and Ki-67 in 41 cases of paraffin embedded RB samples and 10 cases of normal retina were detected by using immunohistochemistry assay, and the statistical analysis of the relationship between the expression of these proteins and sex, clinical stages, optic nerve invasion and tumor differentiation of patients with RB were performed with SPSS 13.0 software.Results The results of immunohistochemistry assay revealed the positive rates of PTEN, MMP-9, Survivin and Ki-67 in RB tissue were 68.3%,60.9%,63.4%and 43.9% respectively. The positive rate of PTEN in RB group largely elevated, and that of MMP-9,Survivin and Ki67 decreased significantly compared with the control group (P<0.05). But all the positive expression of PTEN, MMP-9, Survivin and Ki-67 did not correlate with gender according to the result of Pearson correlation coefficient (p>0.05). The Fisher's Exact Test indicated the expression of MMP-9 in RB positively correlated to clinical stages, but PTEN negatively. The results of Fisher's Exact Test indicated that:the positive rate of PTEN in the intra-ocular growth stage(90.0%) was statistically different with that in the extra-ocular invasion stage (P< 0.05), but not with that in the glaucomatous stage(84.2%), and there was statistical difference for the positive rate of PTEN between in glaucomatous stage and in extra-ocular invasion stage (P< 0.05). The positive rate of PTEN in RB accompanied by optic nerve invasion and was higher than that in RB with no optic nerve invasion (P< 0.05), and that in differentiated RB was higher than in undifferentiated RB, too (P< 0.05). The positive rate of MMP-9 in the intra-ocular growth stage(40.0%) was statistically different with that in the extra-ocular invasion stage (P< 0.05), but not with that in the glaucomatous stage(52.6%), and there was statistical difference for the positive rate of MMP-9 between in glaucomatous stage and in extra-ocular invasion stage (P< 0.05). The positive rate of MMP-9 in RB accompanied by optic nerve invasion and was higher than that in RB with no optic nerve invasion (P< 0.05), and that in differentiated RB was lower than in undifferentiated RB, too (P< 0.05). The positive expression of Survivin was uncorrelated with the sex, clinical stage and tumor differentiation (P>0.05). The positive rate of Ki67 in the intra-ocular growth stage and glaucomatous stage were lower than that in the extra-ocular invasion stage (P< 0.05). The positive rate of Ki67 in RB accompanied by optic nerve invasion and was higher than that in RB with no optic nerve invasion (P< 0.05), and that in differentiated RB was lower than in undifferentiated RB, too (P< 0.05).The results of Spearman's rank correlation indicate that:the coexpression of MMP-9, Survivin and Ki-67 was uncorrelated with the sex of the patients (rs=-0.13, p>0.05), was positively correlate with the clinical stage (rs=0.434, p<0.05) and the optic nerve invasion (rs=0.470, p<0.05), and was negatively correlate with the tumor differentiation (rs=-0.566, p<0.01). The expression of PTEN was negatively correlate with the coexpression of MMP-9, Survivin and Ki-67 (rs=-0.542, p<0.01).Conclusion The significant increase of MMP-9, Survivin and Ki-67 expression and decrease of PTEN expression could be found in RB. The expression and coexpression of PTEN, MMP-9, Survivin and Ki-67 could play an important role in tumor genesis, invasion and metastasis of RB.