| 【Objective】To observe the expression of ER,PR,and Müllerian-related markers(PAX8,PAX2,WT-1)in synovial sarcoma,then to screen out ER/PR-positive subtype of these.Meanwhile,to analyze the correlation between the expression of ER/PR and clinicopathological features and prognosis,and to investigate the origin of ER/PR-positive subtype synovial sarcoma.To observe the expression of ALK and C-met in synovial sarcoma,then to explore its correlation with clinicopathological features and its significance.【Methods】1.82 cases of morphologically and immunohistochemically confirmed synovial sarcoma were made into tissue microarrays via the manual microarray system.2.Separation of SS18 signals was detected via FISH using tissue microarrays of 82 cases synovial sarcoma.3.The expression profiles of ER,PR,and Müllerian-related markers(PAX8,PAX2,WT-1)were determined via immunohistochemical Elivision two-step analysis.4.The expression profiles of ALK(D5F3),ALK(5A4)and C-met was determined via Ventana automatic immunohistochemical staining machine,and ALK/C-met FISH and EML4-ALK RT-PCR were detected in those with over-expression of ALK/C-met protein.【Results】1.A total of 38 synovial sarcoma cases were screened using break-apart SS18 FISH.2.When the positive threshold was ≥5%,11(28.9%)of the 38 cases of SS18 positive synovial sarcoma expressed ER,PR,or both.Statistically significant differences were observed in age,histological grade,and survival between the ER/PR-positive and ER/PR-negative groups(p < 0.05).Follow-up results revealed that the ER/PR-positive group had a significantly better prognosis than the ER/PR-negative group(p < 0.05).When the positive threshold was ≥1%,17(44.7%)of the 38 cases expressed ER,PR,or both.However,statistically significant differences were observed only in histological grade(p < 0.05)between both the groups.All the 38 cases were negative for PAX2 and WT1,and only two(5.3%)cases of ER/PR-negative synovial sarcoma weakly expressed PAX8.3.38 cases of SS18 positive synovial sarcoma,of which the positive rate of ALK(D5F3)was 18.4%(7/38),and the over-expression rate was 2.6%(1/38),but ALK(5A4)all was negative.The only case of over-expression of ALK(D5F3)protein was positive for ALK FISH,but negative for EML4-ALK RT-PCR,and to Pulmonary metastasis.The positive rate of C-met was 18.4%(7/38),and the over-expression rate was 10.5%(4/38).Significant differences were observed in histological classification and histological grade between the C-met positive and negative groups,and the death or metastasis rate of those with over-expression was 75%(3/4).However,all the 4 cases were negative for C-met FISH.4 cases of ALK/C-met over-expression were all ER/PR negative,while 11 cases of ER/PR positive had no over-expression.There was no significant statistical difference between ER/PR and ALK/C-met,but ER/PR positive and ALK/C-met over-expression showed a significant negative correlation.【Conclusion】1.A threshold of ≥5% is more suitable for ER/PR-positive subtype synovial sarcoma.The prognosis of ER/PR-positive subtype synovial sarcoma was significantly better than that of ER/PR-negative subtype synovial sarcoma,suggesting that ER and PR are important prognostic indicators of synovial sarcoma,and this may become an essential basis for endocrine therapy for synovial sarcoma cases.2.No correlation was observed between the origin of ER/PR-positive subtype synovial sarcoma and tumors of Müllerian origin.3.The poor prognosis with ER/PR-negative subtype synovial sarcoma patients of ALK/C-met over-expression.4.The over-expression rates of ALK/C-met suggesting that ALK/C-met may be a potential therapeutic target for ER/PR-negative subtype synovial sarcoma.Therefore,further detection of ALK and C-met protein is recommended for ER/PR negative patients,and clone D5F3 is more suitable for the primary screening of ALK protein. |
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