The Classification Of SYT-SSX Fusion Genes In Synovial Sarcoma And The Correlation Between The Type Of Fusion Genes And Cell Cycle

OBJECTIVE: The aim of this research was to study the classification of SYT-SSXfusion genes in synovial sarcoma (SS), explore their role in SS development and therelationship with cilinical behavior. To investigate the function of fusion genes in cellcycle by immunohistochemical stain .These results would be hoped to elicit a novelpath to discovery the function of the fusion genes in SS.METHODS: The subjects of this study were 54 patients suffered from SS between1974 and 2005. The clinicpathologic data were collected including age, sex, primarytumor site, histologic grading and clinical stage. RNA was extracted from 54 selectedSS embedded by paraffin which express of SYT-SSX fusion genes.The type offusion gene was detected with RT-PCR method. To analyze the relationship of theclinicpathologic features of SS and the type of fusion genes.The microscopic structure of SS was reviewed and choosed the typical domainand manufacture thetissue microarray. The expression level of Ki-67,CyclinD1,CDK4,p21,p27 were examined by immunohistochemistry. Methods of counting:ten representative high visual fields were selected in each slide avoiding of lost areas,and the number of positive staining tumor cells were counted in 100 tumor cells ineach field. Labling index was used to evaluate the entire staining status of each slide.Statistical significance of differences between the SSX1 and SSX2 was calculated byusing chi test and unpaired t test. Statistical software SPSS 11.5 was used in theanalysis. P value less than 0.05 was considered as statistically significant. RESULTS: (1)Among 54-case SS, the male: female ratio was 1.08:1.There were 28male cases and 26 female cases. The age of all the patients was from 9 to 70 years old.The median of age is 36.91 years. The diameter of tumor was from 1 to 29 cm. Themean of diameter was 7.25 cm and the median of it was 5cm. Among 54 cases, therewere 37 patients with tumours on limbs, and there were 17 patients with tumours ontrunk or near trunk. According to the statistic analysis, all of age,sex location of thetumor,the diameter of the tumour were not significantly related to the type of fusiongenes (P＞0.05).(2) Among 54 patients,there were 33 cases with monophasichistologic type,13 cases with biphasic histologic type and 8 cases with poolydifferentiated type. 19 cases of all the patients was in theⅠ～Ⅱstage. Theothers(35) was in theⅢ～Ⅳstage. According to the statistic analysis,Histologic typing were significantly related to type of fusion genes (P＜0.05).Butclinical stage was not significantly related to the type of fusion genes (P＞0.05).(3)There were significant effect of the expression of Ki-67 on the types of fusiongenes(P＜0.05).The LI of Ki-67 in SSX1 was higher than SSX2.(4) There weresignificant effect of the expression of CyclinD1,CDK4,p21 and p27 on the types offusion genes(P＜0.05). The LI of CyclinD1and CDK4 in SSX1 is higher than SSX2and the LI of p21 and p27 is lower than SSX2.(5)Among 54 cases, there were linearcorrelation between CyclinD1 and CDK4,p21(P＜0.05),but cyclinD1 was notcorrelate to the p27 (P＞0.05).CONCLUSIONS: (1) Comparing with sex,age,location of the tumour,traditionalhistologic classification was significant related to the type of fusion genes.SYT-SSX1 and SYT-SSX2 may regulate the differentiation of synovial sarcomaprecursor cells to epithelioid or spindle cells through affecting different target genesor the same target genes at different levels. (2)Increase of the expression of Ki-67 wassignificant in SSX1. Proliferation index of SSX1 is higher than the type of SSX2. (3)The gene of SSX1 could increase the CyclinD1/CDK4 expression and decrease thep21, p27 expression. We hypothesize that SYT-SSX1 and SYT-SSX2 may differ intranscriptional deregulation of one or more key genes involved in mesenchymal toswitch on the cell cycle and escape the mechanism of supervision.