Sexual dimorphism in gastric cancer: tumor-associated neutrophils predict patient outcome only for women

Purpose Tumor-associated neutrophils (TANs) are part of the tumor immune microenvironment (TIME) and may contribute to gastric cancer (GC) biology. We hypothesized that TAN are enriched in the TIME, show sex-specific differences, and correlate with patient outcome. Methods We analyzed the distribution and putative tumor biological significance of TANs in a well-characterized, therapy-naive, European GC cohort using immunohistochemical staining of myeloperoxidase ( MPO), and digital image analysis using Definiens Tissue Studio (R). Results Different tumor compartments were examined, and TAN densities were correlated with various clinicopathological patient characteristics. TAN density showed a large interindividual variability ranging from 0 to 6711.0 TANs/mm(2). Intratumoral distribution patterns were inhomogeneous (tumor surface vs. tumor center vs. invasion front) and correlated significantly with Lauren phenotype, tumor grade, and microsatellite status in the tumor center and invasion front. In the multivariate analysis, TAN density in the invasion front was an independent predictor of tumor-specific survival only for women (HR = 2.77, p < 0.001). In men, no correlation was found between TAN density and survival. Conclusion With regard to TANs, our study independently validates sexual dimorphism in GC biology.