Loss of Stromal Antigen 2 (STAG2) Expression in Upper Urinary Tract Carcinoma: Differential Prognostic Effect According to the Ki-67 Proliferating Index

Abstract

Background

Inactivating mutation and consequent expression loss of stromal antigen 2 (STAG2, also known as SA2), a component of the cohesion complex, is one of the most common genetic aberrations in urothelial carcinoma. However, the clinicopathologic or prognostic significance of STAG2 alterations in upper tract urothelial carcinoma (UTUC) is largely unknown.

Methods

This study immunohistochemically examined the expression of STAG2 in 171 patients with UTUC. The correlations of STAG2 loss with clinicopathologic features and patients' prognoses were examined.

Results

Loss of STAG2 expression was observed in 28 cases (16%). Loss of STAG2 was significantly correlated with histological low grade, papillary architecture, noninvasive tumors, absence of concomitant carcinoma in situ, and lower Ki-67 expression. Loss of STAG2 alone was not significantly associated with patients' prognoses in either the uni- or multivariate analysis. However, STAG2 loss was significantly associated with worse clinical outcome in UTUC with high Ki-67 proliferation indexes, but not in UTUC with low Ki-67 expression.

Conclusions

Loss of STAG2 was generally associated with less aggressive features in UTUC. However, the STAG2 loss was an ominous sign in the subpopulation with higher Ki-67 proliferation indexes. Examining both STAG2 and Ki-67 status may be useful for identifying aggressive clinical behavior of UTUC.

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