Prognostic Significance of Nuclear Accumulation of c-myc and mdm2 Proteins in Synovial Sarcoma of the Extremities

Abstract

We retrospectively analysed a group of primary tumours from 32 patients with synovial sarcomas of the extremities by using immunohistochemistry on paraffin-embedded tissue samples in order to investigate the prognostic significance of the nuclear accumulation of c-myc and mdm2 proteins. Nuclear positive immunostaining for c-myc or mdm2 proteins were revealed in 9/32 cases (28%) and in 6/30 cases (20%), respectively. Since c-myc protein appears to be a key factor for keeping cells in an active proliferative stage, we also analysed the growth compartment of each tumour by using the MIB1 monoclonal antibody, specific for Ki-67 antigen. A high MIB1 index was found in 8/31 cases (26%) but was not associated either with c-myc or mdm2 nuclear positivity. Analysis of clinical outcome was performed in a subgroup of 27 patients with a minimum follow-up of 24 months. Among the clinicopathologic parameters and the biological markers, only the nuclear accumulation of c-myc was significantly associated with a higher relapse rate (p = 0.03). Accordingly, survival analysis confirmed a trend toward a poor event-free survival rate and a worse outcome in c-myc-positive cases (p = 0.12). These data demonstrate that assessment of c-myc nuclear accumulation can be useful to identify high-risk subsets of patients with synovial sarcoma of the extremities.

Prognostic significance of bcl-2, c-myc, survivin and tumor grade in synovial sarcoma

“…Marked tumor necrosis in the synovial sarcoma and high mitotic activity (> 10 mitosis/10 HPF) have been reported as negative prognostic factors (15,16). The mitotic index and the necrosis status of the tumor was associated with survival and disease-free survival and this relationship was statistically significant in our study.…”

“…C-myc expression was found to be associated with survival and c-myc was identified as an independent prognostic factor in multivariate analysis (32). The relationship between c-myc and prognosis was investigated in 27 synovial sarcoma cases with at least 24 months follow-up and c-myc nuclear positivity was reported to be a negative prognostic indicator (33). Although c-myc is a marker expected to give a nuclear reaction, it can also show cytoplasmic staining (34).…”

“…The immune expressions of bcl-2, c-myc and survivin in different types of sarcoma and synovial sarcoma cases and their relationship with the prognosis have previously been investigated (13)(14)(15)(16)(17). Our aim in this study was to immunohistochemically evaluate the relationship between bcl-2, c-myc, survivin expression and the prognosis of synovial sarcoma because literature findings on the relationship of bcl-2 and c-myc immune expression with the prognosis are not clear.…”

Prognostic significance of c-Myc expression in soft tissue leiomyosarcoma

“…In accordance with previous studies, tumors with specific staining in 45% of neoplastic nuclei were scored as positive for c-Myc overexpression. 10 Slides were independently reviewed by two of the authors (ACT and JMMC) blinded to patient outcome; there were no discrepancies in the recorded c-Myc scores.…”

“…[10][11][12] Overexpression of c-Myc has also been described in high-grade liposarcoma, skeletal chondrosarcoma, and uterine leiomyosarcoma. [13][14][15][16] However, the c-Myc oncoprotein has not been studied extensively in other sarcomas, particularly leiomyosarcoma occurring in the somatic soft tissues.…”