Abstract 881: Hyperthermic isolated intraperitoneal chemoperfusion (HIPEC) for treatment of patients with peritoneal carcinosis - Analysing negative influencing cellular mechanisms in the tumor cells.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: In patients with isolated peritoneal carcinosis (PC) of gastric, colorectal and ovarian cancer hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. We analyzed relevant heat shock proteins (HSPs) that confer resistance to physical stress like hyperthermia as well as specific multidrug resistence (MDR) genes in patients with PC. Materials/Methods: Patients with different adenocarcinomas and additional PC that underwent HIPEC therapy between 09/09 and 03/11 in our department (gastric, colorectal and ovarian cancer) were included in the study. HIPEC therapy was performed under specific conditions (1hr permanent chemotherapeutical flux via external pump into the abdominal cavity after resection of relevant tumor masses with elevated temperature up to 43°C). Tumors before and after HIPEC therapy were analyzed for HSPs, ABC transporter and CD133 expression by immunohistochemistry, Western Blot, and RT-qPCR. Additionally, HT29 tumor cells were exposed in vitro to different conditions of hyperthermia up to 43°C for 60 minutes and comparably analyzed. Tumor cells were counted and studied for apoptosis. Results: HSP70/72, HSP90 and CD133 expression was upregulated in the investigated tumors, in particular post HIPEC therapy. Upregulated protein and gene expression was also shown for MDR genes ABCB5, ABCG2 and ABCC5. Hyperthermia induced upregulated protein and gene expression in HT29 tumor cells dependent on incubation temperature, mainly for HSPs observed in western blot, immunohistochemistry and RT-qPCR. Furthermore, cell viability decreased with increasing incubation temperature. Conclusion: Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis inducing cellular effects in patients with PC seem to be negatively influenced by highly conserved HSP mechanisms as well as multidrug resistance genes. Studying HSP and MDR expression profiles both in patient tumors and in vitro are valuable tools to further clarify the effects of hyperthermia and chemotherapeutical agents in context with the treatment of HIPEC therapy in the affected patients. Citation Format: Martin Gasser, Maria Lazariotou, Malte Vetterlein, Tanja Grimmig, Christoph T. Germer, Joerg Pelz, Ana Maria Waaga-Gasser. Hyperthermic isolated intraperitoneal chemoperfusion (HIPEC) for treatment of patients with peritoneal carcinosis - Analysing negative influencing cellular mechanisms in the tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 881. doi:10.1158/1538-7445.AM2013-881