Abstract
Background. SDF-1, and its cognate receptor CXCR4, are recognized as major factors in tumor progression and metastasis. Recent data also suggest that chemokines may play a role in resistance to chemotherapy. In this study, we investigated the expression of SDF-1 and CXCR4 in initial tumor biopsies prior to treatment in patients treated by induction chemotherapy for organ preservation and correlated this expression with response to chemotherapy. Material and Methods. Patients with locally advanced pharyngo-laryngeal carcinomas, candidates for neoadjuvant platinum-based chemotherapy as part of an organ preservation program, were considered for this study. Objective response in organ preservation accounted for more than 50% reduction in tumor size on CT-scan or MRI. Tissue biopsies were scored for SDF-1, CXCR4, Vimentin and E-cadherin staining by immunohistochemistry. Staining was measured according to a specific scoring scale. Biopsies were all read by three different observers for scoring adjudication and quantification was performed using the Histolab Software (Microvision). Results. Among the 42 patients who entered in this study, 23 had primary site in the hypopharynx and 19 in the larynx. Twenty-two patients experienced objective response and 20 patients were non-responders to induction chemotherapy. SDF-1 staining score was higher in cancer cells than that in normal epithelial cells located in the close vicinity of the tumor. SDF-1 staining was predominantly located in the cytoplasm of cancer cells. The level of SDF-1 expression was significantly higher in tumors from non-responders compared to responders (score: 155 vs 110, p=0.01). CXCR4 expression was similar between responders and non-responders, and predominantly located in the cytoplasm and the nucleus of cancer cells. Vimentin and E-cadherin were evaluated as potential differentiation markers. Few tumor cells expressed Vimentin in our biopsies. Interestingly lower E-cadherin expression was observed in non-responders compared to responders (score: 110 vs 170, p=0.01) suggesting that loss in epithelial differentiation may facilitate resistance to chemotherapy in this population. Conclusion. High expression levels of SDF-1 cytokine and the loss of E-cadherin as a marker of epithelial differentiation in cancer cells were shown to correlate with the lack of response to induction chemotherapy in hypopharyngeal and laryngeal squamous cell carcinomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 728. doi:1538-7445.AM2012-728
- ©2012 American Association for Cancer Research
Volume 72, Issue 8 Supplement
