Multivariate evaluation of prognostic markers in synovial sarcoma

Abstract

Aims: Synovial sarcoma (SS) is an aggressive neoplasm but with varied clinical outcomes despite standard treatment protocols. Several clinicopathological features and immunohistochemical stains have been proposed as prognostic markers in SS. The aim of this study was to evaluate SS from a single institution for prognostically relevant clinicopathological and immunohistochemical factors.

Methods: We identified a single-institution cohort of SS with follow-up. Clinical and pathological factors examined included age, sex, tumour location, AJCC (American Joint Committee on Cancer) stage, tumour size, grade and status of surgical margins. Immunohistochemical staining for p16, p53, RB1, MYC, PTEN (phosphatase and tensin homologue), β-catenin, MDM2 and Ki67 proliferative index was performed on tissue microarray. Cox proportional hazard model was used for multivariate assessment of overall survival (OS) and disease-free survival (DFS).

Results: 133 patients with SS met the inclusion criteria for our cohort, with 100 having complete dataset for all study covariates. On Cox regression multivariate analysis, location (axial vs extremity, p<0.001), AJCC stage (p<0.001), p16 expression (≥75%, p=0.021) were significantly associated with worse OS, whereas PTEN intensity (score 2, p<0.001) and p53 expression (null/≥75%, p=0.013) were correlated with improved OS. For DFS analysis, location (axial vs extremity, p=0.030), tumour size (≥5 cm, p=0.009) and MYC expression (≥33%, p=0.013) were associated with inferior outcome. Only PTEN intensity (score 2, p<0.001) correlated with improved DFS.

Conclusions: In reviewing numerous clinicopathological and immunohistochemical markers, this study shows that location, AJCC stage, p16, p53 and PTEN expression were prognostically significant in multivariate analysis for OS in a uniformly treated SS cohort. Location, tumour size, MYC and PTEN expression were significantly associated with DFS.

Keywords: diagnostic techniques and procedures; immunohistochemistry; sarcoma.