Multivariate evaluation of prognostic markers in synovial sarcoma

Correspondence to Dr Ivan Chebib, James Homer Wright Pathology Laboratories, Boston, MA 02114, USA; [email protected]

What is already known on this topic

• Synovial sarcoma (SS) is an aggressive malignancy with tumour location and AJCC (American Joint Committee on Cancer) stage as well-established prognostic indices.

What this study adds

• Multivariate analysis including several immunohistochemical markers shows that p16, PTEN and MYC expression are also statistically significant in overall and/or disease-free survival in this uniform cohort of SS.

How this study might affect research, practice or policy

• Development of prognostic indices in SS should include evaluation of these biomarkers.

• Future evaluation of prognostic markers in SS should be compared against these.

Introduction

Synovial sarcoma (SS) is a mesenchymal neoplasm of uncertain differentiation, characterised by a balanced reciprocal translocation t(X;18).¹ The fusion protein contains a transcriptional activation domain from SS18 and a repressor domain from one of SSX1/2/4.^{2 3} Forty per cent of patients have local recurrence and half will develop distant metastases, with a 5-year survival of 76%–83% for children/adolescents and 60%–76% for adults.^4–10 Moreover, late metastases are possible and series report the 10-year survival in the 55%–61% range.^11–14

Clinical features, including older patient age, large tumour size and proximal location,^{4–10 15–18} as well as pathological features, such as high histological grade,^{19 20} poorly differentiated SS with small round cell change^{21 22} and increased mitoses have been associated with poor prognosis. Recently, several studies with varying results have shown tumour suppressor markers p16/CDKN2A,^{23 24} TP53,^25–28 RB1,²⁵ PTEN (phosphatase and tensin homologue),²⁹ and oncogenes MDM2,^{27 30} MYC,³⁰ may be prognostically significant factors in SS. However, these studies evaluated only a small subset of these markers, typically in univariate analysis, or failed to control for varied clinical confounders, such as treatment.

The objective of this study was to perform a multivariate evaluation of clinicopathological and immunohistochemical prognostic factors for disease-free survival (DFS) and overall survival (OS) in SS from a single institution.

Material and methods

Patients and tissue samples

After institutional review board approval, the surgical pathology laboratory information system and consultation files were searched for cases of SS from January 1990 to September 2017. Three hundred and seventy-seven resection specimens and resected metastatic disease...