High Levels of MFG-E8 Confer a Good Prognosis in Prostate and Renal Cancer Patients

SIMPLE SUMMARY: In the present study, we analyzed the distribution and prognostic impact of milk fat globule-epidermal growth factor-8 (MFG-E8) protein expression in patients with prostate and renal cancers. Our data highlighted MFG-E8 expression by tumor cells in the epithelium. Our results also showed that low levels of MFG-E8 in prostate and renal cancers were associated with worse clinical outcomes. Furthermore, higher numbers of CD206(+) cells were found in the peripheral regions of renal clear cell carcinoma that expressed lower MFG-E8 levels. Globally, our results suggest that MFG-E8 expression could potentially be used as a prognostic marker in prostate and renal cancers. ABSTRACT: Milk fat globule-epidermal growth factor-8 (MFG-E8) is a glycoprotein secreted by different cell types, including apoptotic cells and activated macrophages. MFG-E8 is highly expressed in a variety of cancers and is classically associated with tumor growth and poor patient prognosis through reprogramming of macrophages into the pro-tumoral/pro-angiogenic M2 phenotype. To date, correlations between levels of MFG-E8 and patient survival in prostate and renal cancers remain unclear. Here, we quantified MFG-E8 and CD68/CD206 expression by immunofluorescence staining in tissue microarrays constructed from renal (n = 190) and prostate (n = 274) cancer patient specimens. Percentages of MFG-E8-positive surface area were assessed in each patient core and Kaplan–Meier analyses were performed accordingly. We found that MFG-E8 was expressed more abundantly in malignant regions of prostate tissue and papillary renal cell carcinoma but was also increased in the normal adjacent regions in clear cell renal carcinoma. In addition, M2 tumor-associated macrophage staining was increased in the normal adjacent tissues compared to the malignant areas in renal cancer patients. Overall, high tissue expression of MFG-E8 was associated with less disease progression and better survival in prostate and renal cancer patients. Our observations provide new insights into tumoral MFG-E8 content and macrophage reprogramming in cancer.