PurposeAs mayor biomarkers in tumor microenvironment (TME), tumor associated macrophages (TAMs) of gastric cancer (GC) still needs further studies in terms of the number and distribution pattern.MethodsHerein, tissue microarrays (TMA) incorporating 494 GC surgical samples in duplicate were stained for TAMs infiltration analysis. TAMs number was counted according to the locations, including infiltrating macrophages in cancer nest (MC), in invasive front (MF) and in stroma (MS). Correlations between TAMs number, distribution pattern and clinic-pathological features and survival analyses were performed.ResultsInfiltrating macrophages number in GC tissues was much higher than that in peritumoral tissues. TAMs number was not significantly correlated with the overall survival (OS). TAMs distribution pattern could be categorized into MC or MF/MS dominant pattern, and correlated with histological grade (P =0.001). The median OS of MF/MS dominant pattern (22.1, 95%CI: 23.5-28.9) was significantly shorter than that of MC dominant pattern (25.6, 95%CI: 28.5-35.6) (P =0.002). By receiver operating characteristic curve (ROC) analysis, the predictive value of TAMs distribution pattern was superior to histological grade and pM stage, but inferior to pN and TNM stage.ConclusionsTAMs distribution pattern could be an independent prognostic factor for the OS of GC patients, and patients with MF/MS dominant pattern had worse outcomes.
Purpose
Tumor-infiltrating lymphocytes (TILs) become increasingly relevant to tumor progression. This study aims to evaluate (a) methods of TILs assessment and (b) their prognostic significance in gastric cancer (GC).
Methods
The percentage of stromal TILs (psTIL) was reported semi-quantitatively by H&E evaluation. Herein, we screened two independent cohorts of breast cancer (n=240) and GC (n=481) for psTIL characterization. Correlations between psTIL and clinic-pathological features, as well as overall survival (OS) were further explored. Additionally, the prediction role of psTIL in GC was evaluated by receiver operating characteristic curve (ROC) analysis.
Results
TILs could be demonstrably distinguished from other stromal areas and surrounding tumor nests according to the assessment method. More importantly, it is reproducible, easily to determine, and quickly performed. In GC, a two-grade scale for psTIL was appropriate to be divided into low and high subgroups by using the median value of 10% as the threshold. High psTIL was correlated with no serosa invasion, earlier TNM stage and better survival state (
P
<0.05 for all), and identified as a favorable prognostic factor both by univariate (HR: 0.734,
P
=0.047) and multivariate analyses (HR: 0.722,
P
=0.030). A beneficial OS of high psTIL was found in a linear manner with increasing TILs infiltrates associated with improved survival by Kaplan–Meier survival curve (
P
=0.030) and ROC analysis (AUC: 0.432,
P
=0.012).
Conclusion
TILs provide a reproducible method for assessment that can potentially be used to guide management. The parameter psTIL could be served as an independent, favorable prognostic factor of GC.
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