Methylation Of WIF-1Gene And Expression Of Wnt-5a Protein In Chondrosarcoma

Objective:This research aims to investigate the promoter methylation status of WIF-1gene and the expression of Wnt-5a protein in chondrosarcoma and explore their relationships to clinical and pathological parameters. And then we hope to provide the theory basis for molecular targeting therapy of chondrosarcoma and improve prognosis.Methods:We collected61paraffin embedded tissues of chondrosarcoma and40matched paraffin embedded tissues of chondroma which are all from Shan Dong University affiliated Qi Lu Hospital between2005-2011. The clinical and pathological data was gathered in detail. Methylation specific PCR (MSP) was used to investigate the promoter methylation of WIF-1gene in chondrosarcoma and chondroma. The paraffin embedded samples were made into tissue microarray and immunohistochemical SP method was used to investigate the expression of Wnt-5a protein in chondrosarcoma and chondroma. Then the relationships to clinical and pathological features were explored. SPSS19.0was utilized for statistical analysis. Chi-square test or Fisher’s exact test was used for rate comparison between two groups and established the two-sided test level of significance is P<0.05.Results:1. WIF-1gene promoter methylation was found in17of38(44.74%) chondrosarcoma and5of26(19.23%) chondroma (P=0.035). No significant difference exists in different pathological types, histological grades, invasiveness, ages and sex.2. The positive expression of Wnt-5a protein was observed in chondrosarcoma and chondroma is respectively57.38%(35/61) and12.5%(5/40)(X2=20.341, P=0.000). The expression of Wnt-5a protein in myxoid chondrosarcoma is higher than conventional chondrosarcoma (P=0.016<0.05). And significant difference is found between tumors with infiltration and/or metastasis and that without any invasion and metastasis (P=0.034). Wnt-5a expression is negative in one clear-cell chondrosarcoma sample. The expression of Wnt-5a protein has no relationship to histological grade, ages and sex. Positive expression of Wnt-5a protein was discovered in2of7recurrent patients. But these two samples are both myxoid chondrosarcoma, then we considered that Wnt-5a expression wasn’t related to recurrence of chondrosarcoma.Conclusions:1. The promoter methylation of WIF-1gene may play an important role in the early stage of chondrosarcoma formation and it may contribute to the stimulation of the canonical and noncanonical Wnt signaling pathway.2. The overexpression of Wnt-5a protein is positively related to invasiveness character of chondrosarcoma.3. WIF-1gene promoter methylation, cooperating with overexpression of Wnt-5a protein, may play a key role in the oncogenesis of chondrosarcoma.