Interrelationships between Tumor Proliferative Activity, Leucocyte and Macrophage Infiltration, Systemic Inflammatory Response, and Survival in Patients Selected for Potentially Curative Resection for Gastroesophageal Cancer

Abstract

A number of accepted criteria, including pathological tumor, node, metastasis system stage, lymph node metastasis, and tumor differentiation, predict survival in patients undergoing surgery for gastroesophageal cancer. We examined the interrelationships between standard clinicopathological factors, systemic and local inflammatory responses, tumor proliferative activity, and survival. The interrelationships between the systemic inflammatory response (Glasgow prognostic score, mGPS), standard clinicopathological factors, local inflammatory response (Klintrup criteria, macrophage infiltration), and tumor proliferative activity (Ki-67) were examined by immunohistochemistry in 100 patients (44 esophageal [19 squamous, 25 adenocarcinoma], 19 junctional, and 37 gastric cancers) selected for potentially curative resection. The minimum follow-up was 59months. On multivariate survival analysis, lymph node ratio (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11-2.40, P<0.05), tumor differentiation (HR 2.63, 95% CI 1.45-4.77, P=0.001), mGPS (HR 3.91, 95% CI 1.96-8.11, P<0.001), Klintrup score (HR 3.47, 95% CI 1.14-10.55, P<0.05), and Ki-67 (HR 0.67, 95% CI 0.47-0.96, P<0.05) were independently associated with cancer-specific survival. A higher lymph node ratio was associated with poor tumor differentiation (P<0.05), low-grade Klintrup criteria (P<0.005), and low tumor proliferative activity (P<0.05). Tumor proliferation rate and local and systemic inflammatory responses are important predictors of survival, albeit in a heterogeneous cohort of patients including esophageal, junctional, and gastric cancers. These scores may be combined with accepted tumor-based factors to improve prediction of outcome.