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Tumor infiltration pattern (INF) and tumor origin site were reported to significantly affect the prognosis of gastric cancer (GC), while the immune status under these contexts is not clear. In this study, we correlated the density and phenotype of tumor-infiltrating lymphocytes (TILs) with INF and the tumor origin site to reflect the biological behavior of tumors from a new perspective and also determined their effects on overall survival (OS) and other related clinicopathological features in archival samples of 147 gastric cancers with 10-year follow-up data. We found that the INFc growth pattern (an invasive growth without a distinct border) of GC lacked immune cell infiltration, particularly the cytotoxic T cells and their activated form. It is also significantly associated with an unfavorable prognosis (P < 0.001) and proximal site (P = 0.001), positive lymph nodemetastasis (P=0.002), and later tumor-node-metastasis stage (P < 0.001). Moreover, the density and sub-type of TILs infiltration were significantly different in disparate differentiated areas for the tumor tissue with INFb. Compared with distal gastric cancer, proximal gastric cancers were prone to grow in an INFc pattern (P = 0.001) and infiltrated with fewer TILs, experiencing a shorter survival time (P = 0.013). Multivariate analysis showed that only the INF and the density of TILs were demonstrated to be the independent prognostic factors of OS for the GC. We concluded that GC with an aggressive growth pattern arising from proximal sites always had a weak immune response and resulted in a poor prognosis. The interaction between them and their synergistic or antagonistic effects in the development of tumors need to be further studied. This study opens up a new perspective for research on the biological behavior of the tumor. [ABSTRACT FROM AUTHOR]

Gastric cancer can be classified into three subgroups according to pattern of tumor infiltration into the surrounding tissue: INFa (expanding growth and a distinct border with the surrounding tissue), INFc (infiltrating growth and an indistinct border with the surrounding tissue), and INFb (in-between a and c). How the tumor infiltration pattern (INF) relates to prognosis and type of recurrence in advanced gastric cancer has not been sufficiently explored. We examined 805 consecutive advanced gastric adenocarcinoma patients who underwent curative gastrectomy at our institution between 1980 and 2005. Poor differentiation, serosal invasion, and lymph node metastasis were significantly more frequent in patients with INFc tumors than in those with INFa/b tumors. For patients with a T2 or T3 tumor, there was no significant difference in prognosis between those with INFa/b and with INFc. However, for patients with a T4a or T4b tumor, the prognosis of those with INFc was significantly worse than that of those with INFa/b. In multivariate analysis, INF was an independent prognostic indicator in T4a but not T2, T3, and T4b. Furthermore, the prognosis of T4 patients with INFc tumors was significantly worse than that of those with INFa/b, especially in node-negative but not in node-positive cases. In patients with a T4a or T4b tumor, peritoneal recurrence was significantly more frequent for those with INFc than for those with INFa/b. Our data indicate that INF is useful to predict the prognosis and recurrence pattern in T4a node-negative gastric cancer. [ABSTRACT FROM AUTHOR]