Abstract LB-279: Quantitative assessment of tumor infiltrating neutrophils in primary renal cell carcinoma correlates with presence of metastases.
Authors: Salina Davide , Zaidi Tanweer , Katz Ruth L. 
Published: August 2014

Background: An emerging hallmark of cancer is tumor promoting inflammation. Cancer associated myeloproliferation is a new emerging therapeutic target. Cancers may produce cytokines like G-CSF that recruit neutrophils. The recruitment of neutrophils promotes tumor angiogenesis and suppresses NK cells and cytotoxic T-cells. Cancer patients with leukemoid reactions have higher rates of metastasis. Lung, gastric, ovarian, hepatic, pancreatic, renal and colon cancer are cancers that have been shown to have increased tumor infiltrating neutrophils (TINs). Effectors released from neutrophils, include matrix metalloproteases and elastase, which may support the metastatic dissemination of tumor cells. Elastase degrades E-cadherin, promotes tumor cell dissociation and promotes epithelial to mesenchymal transition in pancreatic tumor cell lines In-vitro. To date there have been no reported studies in humans that have found a role for TINs and associated elastase in promoting tumor progression. Objectives: To study whether the number of TINs and released elastase associated with conventional renal cell carcinoma (RCC) can be used as predictors of tumor progression and patient prognosis. We predicted that RCCs with increased numbers of TINs and extracellular elastase would be associated with advanced tumor stage and decreased overall survival. We wished to evaluate if increased TINs and elastase can be used as a predictor of metastasis and patient survival. Methods: 37 randomly selected cases of primary RCC diagnosed by fine needle aspiration (FNA) from 2002-2005 were analyzed for TINs. TINS were scored on aspirated tissue according to numbers of neutrophils infiltrating a minimum of 50 malignant cells/hpf and scored on a scale of 0-4 (0-1=Low, 2-4=High TIN count). TIN count was correlated with tumor characteristics including size of tumor, Fuhrman's nuclear grade (FNG), presence of metastasis and patient survival data using student t-tests calculations for statistical significance. Results: Of 37 RCCs, 20 cases had high TIN count versus 17 cases that demonstrated a low TIN count. At time of initial FNA, 100% of cases with high TINS had distant metastasis (lungs, liver, bone) whereas only 19% of cases with low TINs showed metastases (p=0.0003). There was a positive linear correlation with the number of distant metastatic sites and numbers of TINs in the primary tumor. Moreover, the mean patient survival time was lower in cases with high TIN counts (32.6 weeks), versus cases with low TIN counts (143 weeks) (p=0.0003). There was no association between numbers of TINS and FNG (p=0.526), or size of tumor (p=0.3) . Neutrophil- associated elastase immunostaining of tumors with high TINs was strongly positive. Conclusion: Our preliminary results indicate that high TIN counts and elastase in primary RCCs appear to be associated with metastases and poor prognosis. TINs may be an independent prognostic factor that can be immediately assessed at time of first biopsy/FNA.

Citation Format: Davide Salina, Tanweer Zaidi, Ruth L. Katz. Quantitative assessment of tumor infiltrating neutrophils in primary renal cell carcinoma correlates with presence of metastases. [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 LB-279. doi:10.1158/1538-7445.AM2013-LB-279