Synovial Sarcoma: Its Chromosomal Aberration Detection And Research On Its Her-2/neu Expression

[Objectives]Synovial sarcoma is a relatively common high grade soft tissue sarcoma,which arises mostly in young adults with high risk of metastasis and recurrence.Diagnoses of synovial sarcoma of morphological variants and unexpected location are usually challenging.As a result,aiming to distinguish synovial sarcoma from other lesions,we analyzed the distinctive features of synovial sarcoma from clinicopathologic,immunohistochemic and genetic aspects.For long period of time,researchers have been craving for the effective therapy against synovial sarcoma.The recently developed against the receptor tyrosine kinases(RTK) such as Her-2/neu may be an alternate candidate.[Methods]We firstly observed the clinicopathological datas of 71 cases of synovial sarcoma including those developed at unexpected location and those with variant mophlogy.To assesse the frequency of expression and potential diagnostic utility of a series of antibodies especially calponin and TLE1,immunohistochemistry was undertaken in paraffin sections from 59 and 55 synovial sarcoma respectively, comparing with 64 and 112 cases of morphologically similar tumors such as MPNST, PNET and SFT et al.Molecular genetically,interphase FISH was utilized in 67 cases of SS and 9 of non-synovial sarcoma with a LSI SYT(18q11.2) dual color, break apart probe.In 53 of the cases,the resultant gene fusion SYT-SSX and its subtype were also analyzed by RT-PCR.51 cases of synovial sarcoma were assesed for Her-2 protein expression by immunohistochemical techniques and 44 of which for quantitative real-time polymerase chain reaction assay.[Results]Of the 71 synovial sarcoma,34(47.8%) arose at unexpected site including pleura,lung,kidney,heart,tibia and etc;30 cases(42.3%) were undifferentiated type;47(66.2%) were monophasic fibrous type,2(2.8%) were monophasic epithelial type and 22(31.0%) were biphasic type.Many cases of unusual sites exhibited unusual morphology.Histologic type had no relationship with the malignancy grade.34.1%synovial sarcoma exhibited immunostain with single antibody of AE1/AE3 or EMA,but 97.7%with both combined.88.0%,77.8%,33.3%cases were positive for Bcl-2,CD99 and S-100 respectively.For calponin antibody,89.8%(53/59) synovial sarcoma cases showed at least focal reactivity,with 26 cases of 2+/3+ and 27 cases of 1+.The immunostain was rather weak in the group of poorly differentiated tumors.It is highly expressed in control tumors derived with relation to smooth muscle or myofirboblastoma,and is seldom expressed in other else.For TLE1 antibody,98.2%(54/55) cases are positive,with 50 cases of 2+/3+,4 cases of 1+ and only 1 case of negative.Despite limited expression of the control group,some kinds of tumors,such as melanoma,mesothelioma,fibromatosis, exhibited high rate of expression.In 66 cases of synovial sarcoma,we obtained definite results in 62(93.9%) by FISH,56 are positive and 6 are negative.More than 80%cells of most positive cases exhibited translocation signal.In the exceptional 1 case,such translocation cells accounted to 30%.Microscopically,tumor cells of this case were limited due to large amount of fibrovascular components among them.2 of unequal signals and 1 of multiple signals(2 orange and 1 green or 3 orange and 2 green) were identified. All of the 3 cases were poorly differentiated with unfavorable outcome,2 of which with available paraffin blocks were proved to be synovial sarcoma by RT-PCR.No SYT aberration was identified in the control group.Detectable mRNA were gained from 86.8%(46/53) synovial sarcoma,41 of which bore SYT-SSX,and 5 negative.The type of transcripts(SYT-SSX1 or SYT-SSX2) had no relationship with histologic type.A total of 44 cases were detected by both FISH and RT-PCR,42 of which got same results.Results from both methods were nearly identical.Her-2 protein expression was detected in 35.3%(18/51) synovial sarcoma, mainly very weak,and strong positive in only 1 case.Higher intensity was present in poorly differentiated synovial sarcoma. Q-PCR demonstrated the presence of mRNA for Her-2 in 23 of 44 specimens. Her-2 mRNA of synovial sarcoma was low level compared with that of breast cancer with DNA amplification.Concentration of the protein did not change with intensity of the mRNA.No evidence of gene amplification was observed.[Conclusions]Synovial sarcoma may occur in any part of the body.Some of the unusual site tumors have overlapping clinicopathological features as well as variant morphology.Combined use of AE1/AE3 and EMA can be very sensitive,rather than other kinds of epithelia markers.TLE1 is high sensitive but not very specific. Comparatively,calponin is also sensitive,and may be used in differential diagnosis if that is not with tumors derived from smooth muscle or myofibroblast.A panel of antibodies including AE1/AE3,EMA,Calponin,TLE1 are recommended as valuable tool in diagnosis of synovial sarcoma.FISH may act as diagnostic aid in problematic cases of SS.Comparing with RT-PCR,FISH takes the advantage of sensitivity,reliability and rapidity of result. As the laboratory and labor costs can be decreased to a great extent,we conclude that FISH is a robust approach and may be more broadly applicable in soft tissue molecular oncology.On the ground of the current research data,we proposed the principles in explanation to FISH results.Abnormalities of FISH signals indicate chromosomal deletion or amplification, which may imply a poor prognosis.As the way Her-2 expressed in synovial sarcoma is greatly different from that in breast cancer,the therapeutic modal against the receptor tyrosine kinases(RTK) such as Her-2/neu may not fit synovial sarcoma well.