The Clinicopathological Features Of Primary Synovial Sarcoma And The Expression Significance Of TLE1 Protein

Background:Synovial sarcoma（SS）is a relatively common malignant tumor in soft tissue,which approximately occupies 10%of soft tissue sarcomas.The name of it arises from its morphological characteristics that are similar with the morphological characteristics of embryonic synovial tissue.But now the origin of its tissue is still not identified.SS commonly appears in young adults,and usually more men than women.The onset position of SS is often in the soft tissues of deep part of limbs,and mostly around the large joint,and also the tumor’s onset position usually has a very close relationship with tendon sheath,synovium and joint capsule.The other onset positions can also be found,and among these positions some are very rare,such as heart,kidney and gastrointestinal track.SS has a feature of bipolar differentiation,it is composited with epithelial cells and spindle cells,and various morphological change can be found.Based on the ratio of cells and degree of differentiation SS can be classified into several types,like bipolar type,single-phase spindle cell type,single-phase epithelial type and low differentiation type.SS’s features include high degree of malignancy,long duration,slow development of the tumor,inconspicuous clinical symptoms and the lack of characteristics performance in imaging.All these features can turn the diagnosis of SS to be very hard and then cause that the tumor can be quite huge when the patients come for a treatment,and even after removal treatment the rates of recurrence and metastasis of SS are very high and thus bring a high death rate.What is more,since SS obtains features which are quite similar with other tumors’,diagnosis of SS is quite a problem to pathological doctors,especially when SS does not appear in the limbs.In this occasion,misdiagnosis can happen and then delay the treatment of patient.Molecular detection is an effective method to help to solve intractable cases.Through some researches,it is found that SS has characteristic changes in molecular genetics,which are t（x;18）（p11.2;q11.2）chromosomal translocation and the subsequent SYT-SSX fusion gene,and SYT gene changes can occur in about 90%of synovial sarcomas.Now“gold standard”of detecting SYT-SSX fusion gene are the molecular detections:fluorescence in situ hybridization（FISH）and reverse transcription-polymerase chain reaction（RT-PCR）,which can effectively improve the objectivity and specificity of synovial sarcoma diagnosis.However,because of the high cost of molecular detection and the difficulty of carrying out the technique,the diagnosis of SS now mainly depends on observing its morphological features and immunohistochemical technique.SSs have a feature of bipolar differentiation,most of them may have CK,EMA and Vimentin positive expression.In the diagnosis of SS,the usually used Bcl-2 and CD99 may have high sensitivity in detection of SS,but they can also be positive in other soft tissue tumors.So even they do have high sensitivity for SS,but lack of specificity,and thus not reliable enough.Based on the facts above,one of the most attractive researches is to find out an immunohistochemistry antibody that has both high sensitivity and specificity to detect SS.Recently as a potential marker for SS,transducer-like enhancer of split（TLE1）is gradually known by pathologists,but its clinical significance is still controversial.Some researchers believe that TLE1 has both high sensitivity and specificity in detecting SS,but others hold an opinion that although the sensitivity is good,the specificity is not enough,which means more evidences are needed to confirm the diagnostic value of TLE1.Objective:This research tried to find out the general characteristics of SS by collecting patients’information,and this research also tried to deepen the cognition of SS by observing and concluding its macroscopic description and morphological features.Authors tried to use immunohistochemistry to observe the expression of TLE1 among a range of SSs which may differ from patients’ages,genders,onset positions or histological types,and the expression of TLE1,Bcl-2 and CD99 in SS,Malignant Peripheral Nerve Sheath Tumor（MPNST）,Solitary Fibrous Tumor（SFT）,Fibrosarcoma and Undifferentiated Sarcoma（US）respectively.Analyze the correlation between histological phenotypes and SYT-SSX fusion gene transcripts in synovial sarcoma.Through these observations above,authors tried to conclude the characteristics of TLE1 expression in SS and other diseases.Methods:1.Sifted 128 confirmed cases of SS that collected from the 1^st Affiliated Hospital of Zhengzhou University during the period from August 2011 to August2017.Basic information of patient,such as age,gender,anatomical part of pathological specimen,imageological examination result and the original pathological report was got from patient’s case and pathological files.Because single-phase and poorly differentiated synovial sarcomas are often indistinguishable from other spindle cell tumors and small round cell tumors,besides the 128 cases,9cases of SFT,10 cases of MPNST and 6 cases of US were also collected and all these were excluded from the possibility of being SS.2.4μm sections were continuously applied on the paraffin embedded tissue,and HE dye was also applied to observe the lesion characteristics and immunohi-stochemical staining.Experiment mainly used immunohistochemistry staining to finish the dye of TLE1,Bcl-2 and CD99 on all the cases collected,and during the experiment SP Immunohistochemistry Two-Step Method was strictly followed.TLE1is positive in nucleus,which would be performed as TLE1 was stained brown yellow or brown.Positive location of CD99 and Bcl-2 are all at cytoplasm or cell membrane.The reports of SYT-SSX fusion gene were obtained from the patients’pathological archives.3.Statistical Method:Using SPSS17.0 to do the analysis.All data were properly classified into different groups（different age,gender,location,subtype and different types of soft tissue tumor）,and then Chi-square Test was exerted to analyze.We hypothesized that there was no difference between the group and the group as a null hypothesis,the statistics held a standard of a=0.05.Results:1.In this research,primary SS has a higher incidence in the age from 40 to 50,and also the ratio of gender in patients is males more than females.The most common incidence positions are limbs,head and neck,and torso.Lung and pleura also perform a relative high incidence of SS.2.There is transition between epithelial cells and spindle cells.Besides the morphological features,thin-walled blood vessels and calcification and may provide promote to the diagnosis of SS.3.The expression of TLE1 does not have difference in ages,genders,incidence positions and morphological types of SS,and thus the difference is statistically insignificant（P>0.05）.TLE1 performs higher positive rate in SS than others soft tissue tumors,and the difference in expression is statistically significant（P<0.05）.Compared with other traditional marker（CD99,Bcl-2）,TLE1 has higher sensitivity（79.7%）and better specificity（56.0%）on detecting SS.Conclusion:1.Familiar with other researches,SS obtains specific clinicopathological features,but in this research,SS has the highest incidence in the ages from 40 to 50.2.In all groups,TLE1 has higher sensitivity and specificity than Bcl-2 and CD99,it performs a good diagnostical value to the SS which is lack of typical biphasic differentiation characteristics.3.Bcl-2 and CD99 may be used as auxiliary antibody to help diagnose SS.