Abstract 1205: Clinical significance of IL-8 receptor expression in esophageal squamous cell carcinoma
Authors: Nishi Tomohiko , Takeuchi Hiroya , Matsuda Sachiko , Irino Tomoyuki , Ueda Masakazu , Saikawa Yoshiro , Kitagawa Yuko 
Published: June 2012

Introduction: Esophagectomy is one of the most invasive surgery for digestive cancer, and the blood level of inflammatory cytokines such as IL-1, IL-6 and IL-8 arise several hours after surgery or in suffering postoperative complications. It is known that postoperative complications are negative predictors in long-term malignancy outcome. It has been reported that IL-8 receptor, one of the chemokine receptor, is expressed on several carcinomas and IL-8 signaling promotes proliferation of cancer cells, however, it is poorly understood in esophageal squamous cell carcinoma (ESCC). In this study, we demonstrate the significance of IL-8 receptor expression and validate the effect of IL-8 receptor expression and postoperative complications on long-term prognosis in ESCC using resected specimens and cancer cell lines.

Materials and Methods: &lt;Immunohistochemical analysis&gt; Eighty-two specimens were sectioned from archived, paraffin-embedded tumor tissues obtained from patients with ESCC underwent esophagectomy and extended lymphadenectomy to have no residual cancer in our institute between 1997 and 2002. These were stained using polyclonal antibody to IL-8 receptor, and correlation between stainability and disease-free survival as well as overall survival was examined. &lt;in vitro&gt; TE4, the human ESCC cell line with the high expression of IL-8 receptor at protein levels and TE11, the one with the low expression were cultured at 1×105cells/mL in medium. Cells were transferred to the 96-well microtitre plates containing diluted IL-8. Plates were incubated for indicated periods and WST assay was performed to evaluate the proliferation of ESCC cells. &lt;in vivo&gt; Four groups of 5 nude mice were injected subcutaneously in the dorsal flank with 3×106 cells (TE4, TE11), and 1 of 2 groups were received intraperitoneal (i.p.) injection of 300ng of IL-8 everyday. Tumor volume was measured twice weekly with a caliper in 2 weeks.

Results: &lt;Immunohistochemical analysis&gt; IL-8 receptor was expressed in 33 specimens of 82 (40.2%). The patients with IL-8 receptor expression in primary tumor had shorter disease-free survival compared to those with negative expression. Especially, the patients with IL-8 receptor expression who suffered postoperative complications such as pneumonia and ruptured suture had a poorer prognosis (p=0.013). &lt;in vitro&gt; TE4 cells in IL-8 administered group proliferated significantly more than those in control group (p&lt;0.001) but TE11 showed no significant difference. &lt;in vivo&gt; Tumor growth of TE4 in i.p. group was significantly larger than that in control group (p=0.028).

Conclusion: Our results suggest that the expression of IL-8 receptor is associated with the proliferation of ESCC. The patients with IL-8 receptor expression who suffered postoperative complications probably need strict follow-up and aggressive adjuvant therapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1205. doi:10.1158/1538-7445.AM2011-1205