Stathmin is an Independent Prognostic Marker of Poor Outcome in Uterine Leiomyosarcoma

Abstract

The objective of this study was to analyze the expression and prognostic role of cancer-associated proteins in uterine leiomyosarcoma (uLMS). p53, DAXX, ATRX, HMGA2, IMP3, Stathmin, and phospho-Stathmin (p-Stathmin) protein expression by immunohistochemistry was analyzed in tissue microarrays from 244 uLMS. Expression was assessed for association with clinicopathologic parameters in 173 patients with available data. Tissue microarrays were informative in 230 cases. p53 was aberrant in 44% of tumors. DAXX, ATRX, HMGA2, IMP3, and Stathmin were expressed in 90%, 55%, 40%, 33%, and 97% uLMS, respectively. Cytoplasmic and nuclear p-Stathmin staining was seen in 77% and 68% of tumors, respectively. Stathmin expression was significantly related to higher mitotic count (P < 0.001), a higher degree of atypia (P = 0.006), and vascular invasion (P = 0.016), whereas p-Stathmin expression was significantly related to advanced stage (P < 0.001), higher mitotic count (P < 0.001), and vascular invasion (P = 0.001). In univariate survival analysis for 165 patients with informative tissue microarrays, aberrant p53 (P = 0.026) and higher IMP3 (P = 0.024), Stathmin (P < 0.001), cytoplasmic p-Stathmin (P < 0.001), and nuclear p-Stathmin (P < 0.001) expression was associated with poor disease-specific survival. Clinicopathologic parameters significantly related to poor disease-specific survival were older age (P = 0.006), extrauterine disease at diagnosis (International Federation of Gynecology and Obstetrics (FIGO) stage ≥2; P < 0.001), high mitotic count (P = 0.02), and grade 2 to 3 atypia (P = 0.017). In multivariate analysis, age (P = 0.002), FIGO stage (P < 0.001), and Stathmin expression (P < 0.001) were independent prognosticators. Stathmin was the only prognosticator in a multivariate analysis limited to patients with FIGO stage I disease (P = 0.013). In conclusion, Stathmin expression is strongly associated with poor survival in uLMS and may be a new prognostic marker in this malignancy.