Prognostic value of fibrosis ratio in metastatic lymph nodes of node-positive advanced gastric cancer

Lymph node metastasis plays a crucial role in predicting prognosis in advanced gastric cancer (AGC). In the present study, we formulated a fibrosis ratio (FR), defined as the number of metastatic lymph nodes with fibrosis divided by the total number of lymph nodes, and sought to determine whether it can be used to predict the prognosis of patients with AGC and improve on existing node staging. We retrospectively analyzed 161 patients who underwent curative resection for node-positive AGC between 2001 and 2010, evaluating the association between FR, lymph node ratio (LNR), and micrometastasis, and the relationship between FR and clinicopathologic findings, overall survival (OS) and disease-free survival (DFS). A high FR was significantly related to T stage (P < .001), N stage (P < .001), tumor stage (P < .001), lymphatic invasion (P < .001), and venous invasion (P = .007). FR was significantly correlated with an increased number of metastatic lymph nodes (P = .001, R = 0.869) and LNR (P = .001, R = 0.943), but not with total harvested lymph nodes. Patients with micrometastases had a lower FR, compared with those without micrometastases (P < .001). A survival analysis showed poor OS for patients in the entire cohort (P < .001); N1 (P = .002), N2 (P = .004), N3a (P = .010), and N3b (P = .003) stages; and groups with high LNR (P = .013) and low LNR (P = .001). DFS was also poor for the entire cohort (P < .001) and the N2 (P = .013), N3b (P = .002), high-LNR (P = .036), and low-LNR (P = .001) groups, but not the N1 or N3a group. Univariate and multivariate analyses revealed that high FR was an independent prognostic factor for OS (hazard ratio [HR], 2.780; CI, 1.655-4.670; P < .001) and DFS (HR, 2.051; CI, 1.199-3.508; P = .009) in AGC. Collectively, our findings indicate that high FR is associated with adverse clinicopathologic parameters in AGC, clearly establishing nodal fibrosis as a pathological finding with value in predicting poor prognosis of patients with AGC. Thus, combining current N stage and LNR diagnostics with FR could improve prognostic prediction in AGC.