The Diagnostic And Prognostic Value Of SYT-SSX And Their Role In The Development And Progress In Synovial Sarcoma

BackgroundThe diagnosis and differential diagnosis of synovial sarcoma are difficult forpathologists. Moreover, the reports about prognosis of synovial sarcoma arecontradictory. The translocation t(X;18)(p11.2;q11.2) leads to the fusion of SYT andSSX gene. The t(X;18)(p11.2;q11.2) and SYT-SSX fusion gene are moleculargenetics features and may play an important role in the development and progressionof synovial sarcoma. In addition, detecting SYT-SSX is useful for the diagnosis andprognosis of synovial sarcoma.ObjectiveTo assess the value and applicable condition of molecular genetics detection ofSYT-SSX for diagnosis of synovial sarcoma, and supply experimental evidence for itsclinical use. To analyze the prognostic role of SYT-SSX fusion type and someclinicopathologic parameters, and find some factors indicating prognosis anddirecting therapy in synovial sarcoma. Furthermore, to initially study the role ofSYT-SSX in epithelial differentiation and tumor cell proliferation and apoptosis, andsupply experimental basis for explaining the mechanism of development andprognosis of synovial sarcoma.Methods1. (1) One hundred ninety-five potential synovial sarcomas were collected andclassified according to clinical feature, histological morphology andimmunohistochemistry staining. (2) Tissue microarrays were made. SYT-SSX fusiongene was tested by FISH on tissue microarrays. (3) RNA was extracted fromparaffin-embedded tissue, and SYT-SSX mRNA expression was detected by RT-PCR.(4) The results of traditional diagnosis and molecular genetics were compared at last.2. (1) SYT-SSX1 and SYT-SSX2 mRNA expression were detected by RT-PCR. (2) Immunohistochemistry staining was performed for E-cadherin, a-catenin,β-catenin,γ-catenin, Ki-67, Bcl-2 and Bax. (3) Apoptosis was analyzed by TUNEL.(4) The relations between SYT-SSX fusion type and histological type, expression ofCK, EMA, E-cadherin and catenins, Ki-67 labeling index, apoptosis index andexpression of Bcl-2 and Bax were analyzed in the end.3. (1) The survival rates and median survival time of patients with synovialsarcoma were calculated by life. table method. (2) The relations of SYT-SSX fusiontype and some clinicopathological parameters with overall survival, recurrence-freesurvival and metastasis-free survival of patients were studied by univariate andmultivariate analyses.Results1. (1) According to clinical feature, histological morphology andimmunohistochemistry staining, 62 (31.8％), 49 (25.1％) and 84 (43.1％) cases wereclassified into synovial sarcoma with certain diagnosis, with probable diagnosis andwith possible diagnosis, respectively. (2) 168 cases (86.2％) could be analyzed byFISH, and 138 (70.8％) were positive for SYT-SSX fusion gene. (3) 179 cases (91.8％)could be analyzed by RT-PCR, and 140 (78.2％) were positive for SYT-SSX mRNAexpression. (4) 164 cases were positive for SYT-SSX fusion gene or mRNAexpression. The coincidence rate of FISH and RT-PCR results was 84.8％. (5) 91.9％of synovial sarcoma with certain diagnosis, 85.7％of probably diagnostic synovialsarcoma and 77.4％of possibly diagnostic cases were positive for SYT-SSX.2. (1) In 145 synovial sarcomas with SYT-SSX, 50 (34.5％) were SYT-SSX1,and 91 (62.8％) were SYT-SSX2. Moreover, none is positive for both SYT-SSX1 andSYT-SSX2. (2) The rate of biphasic type (P＜0.001) and positive rates of CK(P=0.012), EMA (P=0.047), E-cadherin (P＜0.001), catenins (P＜0.001) inSYT-SSX1-positive cases were significantly higher than those in SYT-SSX2-positive ones. (3) The numbers of mitosis in SYT-SSX1 and SYT-SSX2 type of synovialsarcomas were 15.58±9.18 and 11.02±8.78, respectively. Furthermore, their Ki-67labeling index were 25.26％±12.78％and 19.77％±11.44％, respectively. Thenumbers of mitosis (P=0.004) and Ki-67 labeling index (P=0.010) inSYT-SSX1-positive cases were significantly higher than those in SYT-SSX2-positiveones. (4) The apoptosis index in SYT-SSX1- and SYT-SSX2-positive cases were1.66％±1.84％and 1.65％±2.22％, respectively. There is not significant differencebetween them. In addition, there is not significant difference of Bcl-2 and Baxexpression between SYT-SSX1 and SYT-SSX2 type of synovial sarcomas.3. (1) The 1-, 3-, 5- and 10-year overall survival rates of 141 patients were88.01％, 75.11％, 57.82％and 27.72％, respectively. The 1-, 3-, 5- and 10-yearrecurrence-free survival rates were 19.77％, 40.39％, 50.68％and 70.10％,respectively. The 1-, 3-, 5- and 10-year metastasis-free survival rates were 12.69％,23.51％, 37.20％and 55.43％, respectively. (2) The overall survivals of patients withtumor size≥5cm,Ⅲgrade, SYT-SSX1 type and metastasis were poor. Furthermore,the recurrence-free survivals of patients with tumor size≥5cm andⅢgrade werepoor. In addition, the metastasis-free survivals of patients with tumors outside ofextremities,Ⅲgrade and SYT-SSX1 type were poor.Conclusion1. (1) To examine SYT-SSX fusion gene by FISH and test SYT-SSX mRNAexpression by RT-PCR in paraffin-embedded tissue are helpful for the diagnosis ofsynovial sarcoma. (2) The molecular genetics detections of SYT-SSX are notnecessary and should be used when diagnosis is difficult with traditional methods.2. (1) SYT-SSX1 and SYT-SSX2 are alternative in synovial sarcoma. Theremay be difference of the rate of SYT-SSX1 to SYT-SSX2 in different regions andraces. SYT-SSX2 may be more than SYT-SSX1 in Chinese patients with synovial sarcoma. (2) The ability of SYT-SSX1 pertaining or promoting tumor cells todifferentiate to epithelium is stronger than that of SYT-SSX2. They possibly affectdifferentiation of tumor cells by controlling expression of down-stream genes. (3) Theability in controlling tumor cell proliferation of SYT-SSX1 and SYT-SSX2 isprobably different. However, there is not significant difference of their effect toapoptosis in synovial sarcoma.3. (1) Tumor size, histological grade, SYT-SSX fusion type and metastasis areimportantly and independently prognostic factors for patients with synovial sarcoma.(2) Tumor size and histological grade have relation to recurrence of synovial sarcoma.(3) Tumor site, histological grade and SYT-SSX fusion type have relation withmetastasis of synovial sarcoma. (4) Histological grade should be indicated inpathological reports. Moreover, SYT-SSX fusion type can be detected to assesspatients' prognoses if there is technique condition.