Abstract 10: Comparison of outcomes in patients undergoing rectosigmoid resection: End colostomy versus reanastomosis

Abstract

9: Identification of molecular markers for targeted treatment of uterine sarcoma J. Shank, J. Rhode, J. Liu. University of Michigan, Ann Arbor, MI, USA, Monarch Women's Cancer Center, Salt Lake City, UT, USA Objectives: Uterine sarcomas are rare and aggressive tumor types. Patients diagnosed with this disease often have poor clinical outcomes, despite multi-modal therapy. Because uterine sarcomas are not common, investigations into novel therapeutics for this disease have been limited. The aim of our study was to identify the expression of therapeutic targets using tissue microarrays in order to direct the exploration of molecularly targeted treatment. Methods: Tumor tissue was collected from 36 patients with uterine sarcomas (6 endometrial stromal sarcomas [ESS], 7 leiomyosarcomas [LMS], and 23 carcinosarcoma [CS]) who were evaluated at a single cancer center between 1996 and 2004. Tissue microarrays were constructed and expression of several molecular markers that are associated with targeted therapeutics in current use for other tumor types was assessed. Expression of VEGF, EGRF, c-Kit and HER-2 was investigated using immunohistochemistry. Immunostaining was evaluated by a gynecologic pathologist. Clinical outcomes including demographic data, treatment modalities received, and overall survival were recorded. Results: The mean age of patients included in this study was 63 (range 35–91). Expression of VEGF, EGFR, c-KIT, and HER-2 was detected in 81%, 81%, 72%, and 14% of all uterine sarcomas examined respectively. VEGF was expressed in 17% of ESS (1/6), 86% of LMS (6/ 7), and 96% of CS (22/23). EGFR was expressed in 50% of ESS (3/6), 86% of LMS (6/7), and 87% of CS (20/23). Expression of c-KIT was seen in 50% of ESS (3/6), 57% of LMS (4/7), and 83% of CS (19/23). HER-2 expression was minimal in all tumor types (ESS 17% [1/6], no expression in any LMS samples, and CS 7% [4/23]). Conclusions: Our data suggests that anti-angiogenic therapy may have activity in uterine leiomyosarcomas and carcinosarcomas. Targeted therapy for EGFR may have significant effects in patients with LMS and CS. This finding may justify using monoclonal antibodies against EGFR (such as cetuximab) or small molecule inhibitors of EGFR (such as gefitinib) in patients with LMS and CS. c-KIT also may be a potential target in CS and further studies with imatinib may be justified. HER-2 is a poor therapeutic target in all three types of uterine sarcomas. These results provide rationale for the use of targeted therapy to improve outcomes for uterine sarcoma