| ObjectiveIn order to search for new molecular markers as prognostic factors in synovial sarcoma and to provide more information for clinical practice, guiding treatment and reducing recrudescence or metastasis, the following biologic markers as E-cad,β-cat, P27, CyclinD1, MT, Ki-67 and EGFR were investigated. Furthermore, their relevance to tumor biological characteristics and survival time after operation of patients were analyzed.Materials and methodsOur study is a retrospective investigation. Eighty eight cases of synovial sarcoma from May 1993 to May 2006, in the department of Pathology, General Hospital of PLA were collected and reviewed by surgical resection, formalin fixed, embedded in paraffin, two cases from the autopsy, total 90 cases. Through read HE staining biopsy slice and immunohistochemistry, our ruled out suspicious samples and obtained 83 cases. According to the criteria of synovial sarcoma Histologic Typing of Bergh, searched relevant cases and follow-up. Finally, a total of 60 cases of synovial sarcoma with complete clinical data and follow-up information were enrolled in the study.Immunohistochemistry: The seven biologic markers-E-cad,β-cat, P27, CyclinD1, MT, Ki-67 and EGFR expression were detected in 60 cases of synovial sarcoma by PV6000 immunohistochemical method. Their relationships to clinical pathology and prognosis were also analysed.Somatic Mutations of EGFR gene: EGFR mutation status was detected by DNA extraction and PCR-sequences in 20 cases of paraffin-embedded synovial sarcoma.Results 1. Expression of biologic markers and their relation with clinicopathological parameters and survival rate in synovial sarcoma1) The positive expression rates of biologic markers were as follows: E-cad 28.3% (17/60) ,β-cat 23.3% (14/60) , the abnormal expression rate ofβ-cat 45% (27/60), P27 45% (27/60), CyclinD1 40% (24/60), MT56.6% (34/60), Ki-67 46.6% (28/60) ,EGFR28.3% (17/60) .2) Among them E-cad,β-cat and the abnormal expression rate ofβ-cat were related to histologic typing. The expression of E-cad andβ-cat showed a negative correlation with histologic typing while the abnormal expression rate ofβ-cat was on the contrary. The expression of E-cad andβ-cat in biphasic type were significantly higher than that in monophasic type and poorly differentiated type (P <0.05) while the abnormal expression rate ofβ-cat was on the contrary (P =0.001 ) .In addition, the expressions ofβ-cat was negative, positively corresponding to tumor grade fromⅡtoⅢ(P =0.025) .The abnormal expression rate ofβ-cat presented a increased correlation with the tumor grade, but which was not significant. The abnormal expression rate ofβ-cat in limbs were significantly higher than that in trunk (P =0.004) , increased correlation between the abnormal expression rate ofβ-cat and clinical stage (TNM) was showed significant (P =0.007) , the abnormal expression rate ofβ-cat in patients with distant metastasis were higher than in those without distant metastasis (P =0.000). E-cad andβ-cat were on the contrary, but which was not significant.The positive expression ratios of P27 in patients without distant metastasis was higher than in those with distant metastasis (P=0.025) and presented a negative correlation with the distant metastasis, CyclinDl was on the contrary (P <0.05). The expressions of P27 was negative, positively corresponding to tumor grade (P=0.044)while P27 presented a negative correlation with the tumor grade.The positive expression ratios of Mt and Ki-67 in patients with distant metastasis were higher than in those without distant metastasis (P <0.05) and presented a positive correlation with the distant metastasis. In addition, Ki-67 presented a positive correlation with the tumor diameter(P=0.047). The expression of MT showed a positive correlation with the tumor grade and clinical stage (TNM), the expressions of MT was increased, positively corresponding to tumor grade and clinical stage (TNM) (P <0.05) . The expressions of EGFR was not correlation with patient gender, age, tumor diameter, location, typing, tumor grade , clinical stage (TNM)and metastasis (P>0.05) .3) By univariant survival analysis, MT, P27, E-cad, the abnormal expression rate ofβ-cat, Ki-67, TNM stage, tumor grade and distant metastases all showed significant correlation to prognosis. Negative correlation between TNM stage, tumor grade and survival time after operation was showed significant (Ptnm =0.000, Pgrade =0.048) , survival time after operation with nonmetastases was better than with metastases (P =0.000), survival time after operation with MT and Ki-67 negative expression was better than with positive expression (P mt=0.010, P Ki-67=0.027), survival time after operation with P27 positive expression was better than with negative expression (P=0.008), survival time after operation with E-cad positive expression was better than with negative expression (P=0.042), survival time after operation with the abnormal expression rate ofβ-cat negative expression was better than with positive expression (P=0.002) and survival time after operation withoutβ-cat abnormal expression was better than with abnormal expression (P =0.007). In Cox multivariant survival analysis, MT, P27 and distant metastases were independent prognostic indicators for survival time after operation in synovial sarcoma. The negative expression of MT, positive expression of P27 and nonmetastases indicated longer a survival time, better prognosis.2. Mutations of EGFR gene in synovial sarcomaIn 20 cases of synovial sarcoma, the two cases immunohistochemistry results showed that the expression of EGFR-positive cases after a sequence analysis, mutation rate of 10 percent. One case of EGFR gene No. 20 Exon has a missense mutation, point mutations at codon 796 of the 2386 base (GGC→AGC) , glycine into serine (Gly→Ser) . One case of EGFR gene No. 19 Exon has a missense mutation, point mutations at codon 731 of the 2191 base (TGG→CGG) , tryptophan into arginine (Trp→Arg) . In addition, two cases detected EGFR gene mutations have taken place synonymous(the immunohistochemistry show: one case of positive expression of EGFR gene expression, one case of negative expression), the mutation rate of 10 per cent. One case of EGFR gene No. 20 Exon has a synonymous mutation, point mutations at codon 787 of the 2361 base (Gln: CAG→CAA) .One case of EGFR gene No. 18 Exon has a synonymous mutation, point mutations at codon 725 of the 2175 base (Thr: ACG→ACA). The existence of mutations in the tyrosine kinase domain of the EGFR gene in a small subset of synovial sarcomas suggests that only few patients may profit from the tyrosine kinase inhibitor therapy. Therefore, a large sample studies needed to further explore and confirm.Conclusions1 MT, P27 and metastases were independent prognostic indicators in synovial sarcoma.2 The expression of E-cad,β-cat, P27, CyclinD1, MT and Ki-67 related to distant metastasis. The adhesion among cells was reduced and the motility of tumor cells was increased by the decreased expression of E-cad, the abnormal expression ofβ-cat. P27 regulate the cell cycle process restrictive. It is suggested that the expressions of above-mentioned biologic markers may play an important role in the development and progression of the tumor and they may become new prognostic markers for synovial sarcoma.3 Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial sarcoma, require substantial further explored and confirmed samples... |
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