Ezrin immunohistochemical expression in advanced soft tissue sarcoma biopsy specimens from patients treated in a phase II trial of dose-dense doxorubicin- and ifosfamide-based chemotherapy

e21508 Background: Ezrin is a member of the ERM (ezrin, radixin, moesin) protein family and links F-actin to the cell membrane, and it is involved in regulating growth and metastatic behaviour of cancer cells. Ezrin expression is associated with tumor progression and metastasis in several cancers, including sarcomas. This study evaluated ezrin expression as a predictor of response to chemotherapy and as a prognostic factor in soft tissue sarcoma (STS) patients (pts) treated in a dose-dense schedule protocol. Methods: 21 chemotherapy-naïve pts diagnosed with high-grade STS, not candidates for a limb-sparing surgery, were enrolled in a prospective phase II study of a sequential and dose-dense regimen consisting of doxorubicin 30 mg/m2 d1–3 q2w and ifosfamide 2.5 g/m2 d1–5 q3w, 3 cycles each, with G-CSF support. Ezrin expression was analyzed by immunohistochemistry on slides from formalin-fixed, paraffin-embedded, primary tumor biopsy blocks, with the anti-ezrin antibody clone AB-1(3C12) (NeoMarkers). Cytoplasmic immunostaining in more than 10% of tumor cells was considered as positive. Ezrin expression was correlated with response rate, progression-free (PFS) and overall survival (OS). Results: Leiomyo-, synovial and sarcoma NOS were the most frequent subtypes (5 pts each). 13 out of 21 pts (62%) presented distant metastasis. Protocol was halted after 3 toxic deaths. Three pts achieved partial response (RR 14%). With a median follow-up of 11.7 mo, median PFS and OS were 8.9 and 20.1 mo, respectively. In univariate analysis, OS was higher for synovial sarcoma pts (not reached vs. 14.2 mo, HR 0.0, 95%CI 0.06–0.82, p=0.02), and for those aged 45 y or less (20.1 vs. 4.2 mo, HR 0.30, 95%CI 0.03–0.88, p=0.04). Ezrin expression was available for 20 pts: it was positive in 9 pts (45%) and negative in 11 pts (55%). Ezrin expression was not related to tumor response (p = 0.40), and no significant association was detected between ezrin expression and median PFS or OS. Conclusions: Expression of ezrin was not a useful marker to predict outcomes in STS pts treated with dose-dense doxorubicin- and ifosfamide-based chemotherapy. No significant financial relationships to disclose.