GST‐P1 as a histological biomarker of synovial sarcoma revealed by proteomics

Abstract

Synovial sarcoma have two histological subtypes, biphasic and monophasic, defined respectively by the presence or absence of glandular epithelial differentiation. To develop histological biomarkers for synovial sarcoma subtypes, we examined the proteomic profile using two-dimensional difference gel electrophoresis. We identified 29 protein spots whose intensity was statistically different between the monophasic (15 cases) and biphasic (9 cases) subtypes (p ,0.01). Mass spectrometric protein identification demonstrated that these 29 spots corresponded to 24 distinct gene products involved in cytoskeletal organization, trsnscription/trsnslation, protein/ collagen binding, and ion transport, as well as structural constituents of the epidermis. Two of the 29 spots derived from glutathione S-transferase P (GST-P1) had higher intensity in biphasic type. Immunohistochemistry on additional 42 synovial sarcoma cases revealed that positive expression of GST-P1 was observed in 10 of 12 biphasic (83.3%), in 4 of 27 monophasic (14.8%) and in 1 of 3 poorly differentiated synovial sarcomas (p = 0.0002). Among the clinico-pathological parameters examined, GST-P1 expression significantly correlated only with the histological subtype. GST-P1 had more discriminative power than the status of fusion genes SYT-SSX1 and SYT-SSX2, previously reported to be correlated with the histological subtype. These results establish GST-P1 as a histological biomarker candidate for synovial sarcoma differentiation into subtypes.

Proteomic analysis of soft tissue sarcoma

“…In addition, our proteomic study, which provided the protein expression profiles for the histological subtypes of synovial sarcoma by 2D-DIGE, identified only the GST-P1 expression to significantly correlate with the histological subtype, while also confirming that the biphasic type had a higher GST-P1 expression in the other subtypes according to an immunohistochemical study [21].…”

“…We routinely employ 2D-DIGE for biomarker identification [11,13,21,22,27,28,30,36,37]. 2D-DIGE is an advanced variation of 2D-PAGE (two-dimensional polyacrylamide gel electrophoresis), and has the potential to overcome many drawbacks of classical 2D-PAGE ( Fig.…”

“…These tumors are mainly characterized by the presence of a chromosomal translocation, t(X;18)(p11.2;11.2), representing the fusion of the SYT gene with SSX1, SSX2 or SSX4 [1]. There have been two papers that have provided protein expression profiles of synovial sarcomas according to the classification of histological subtypes and the identification of prognostic biomarkers (Table 1) [21,30].…”

“…In data analysis, the protein spots whose intensity is statistically different between the groups examined are identified using the Wilcoxon test, hierarchical clustering, principal component analysis, correlation matrix studies, and support vector analysis using datamining software (Fig. 1c) [11,13,21,22,27,28,30]. Proteins corresponding to the spots of interest are identified by mass spectrometry.…”

“…Proteomic technologies have also identified some candidate proteins associated with differential diagnosis [11,13,[21][22][23][24][25][26], prognosis [27][28][29][30][31], and response to chemotherapy [11,32] in bone and soft tissue sarcomas (Table 1).…”