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

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/translation, 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.