Macrophage Inflammatory Protein-3α Is Downregulated in Clear Cell Renal Cell Carcinomas and Correlates with Stage and Grade
Enrico Munari, Justin S Poling, Nilda D Gonzalez Roibon, Sheila F Faraj, Michele Doucet, Alcides Chaux, Scott Kominsky, Kristin L Weber, Georges J Netto. Johns Hopkins Hospital, Baltimore, MD; Universidad del Norte School of Medicine, Asuncion, Paraguay
Background: Macrophage inflammatory protein-3α (MIP-3α, aka CCL20) is an inflammatory and homeostatic chemokine that interacts with the CCR6 receptor to attract immature dendritic cells and lymphocytes. Studies have shown upregulation of MIP-3α in pancreatic, breast, cervical, hepatocellular, and hematopoietic malignancies. Increased expression of MIP-3α has also been demonstrated in renal transplant specimens with rejection, but the expression of MIP-3α has not been studied in clear cell renal cell carcinoma (CCRCC).
Design: Immunohistochemistry for MIP-3α was performed on microarrays that contained matched primary CCRCC and normal kidney specimens (n=133) spotted in triplicate, as well as unmatched metastatic CCRCC specimens (n=40). Each spot was assigned an H-score (percentage of cells expressing MIP-3α x intensity of expression) by a pathologist. Statistical analysis was performed using STATA to calculate Kruskal-Wallis equality-of-populations rank test results.
Results: MIP-3α expression was downregulated in both primary and metastatic CCRCCs as compared to normal kidney (p=0.0001) by both H-score and percentage of cells expressing MIP-3α independent of intensity. Expression did not differ between primary and metastatic CCRCCs (p=0.525). The H-score showed positive correlation with tumor stage (p=0.0173) and Fuhrman grade (p=0.0009) of primary CCRCCs, but did not correlate with overall survival, disease-specific survival, or disease progression. Percentage of cells expressing MIP-3α showed positive correlation with Fuhrman grade (p=0.0337), but not tumor stage, overall survival, or disease-specific survival. In metastatic CCRCCs, the H-score inversely correlated with disease-specific survival (p=0.0349).
Conclusions: In primary and metastatic CCRCCs expression of MIP-3α is downregulated as compared to normal kidney, suggesting a possible difference in the role of dendritic and inflammatory cells in CCRCCs as compared to other malignancies where MIP-3α has been found to be upregulated. In primary tumors, increased expression of MIP-3α is correlated with tumor stage and Fuhrman grade. Our finding of inverse correlation of MIP-3α expression in metastatic tumors with survival merits further investigation.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 189, Tuesday Afternoon