Identification and Validation of Lymphovascular Invasion as a Prognostic and Staging Factor in Node-negative Esophageal Squamous Cell Carcinoma.

Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increase risk of micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy.Using a prospective database of patients with ESCC, 666 cases were retrospectively analysed to identify the relationship between LVI and survival, and to evaluate prognosis predictive accuracy after combining LVI and TNM system. Pathological slides were re-assessed by gastrointestinal pathologists according to the strict criteria. 1000-bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database for external validation.LVI was present in 33.8%, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease-specific survival (DSS; HR=1.59; 95% CI, 1.30-1.94) and disease-free survival (DFS; HR=1.62; 95% CI, 1.32-1.98) after T classification. Among node-negative patients, LVI and T classification were two independent predictors of DSS and DFS (p<0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8% (p<0.001), respectively. The external validation showed congruent results. The DSS of TxN0MO with LVI was similar to the corresponding TxN1M0 (all p>0.05). In contrast, LVI was not associated with DSS or DFS among node-positive patients.The independent prognostic significance of LVI only existed in node-negative patients with ESCC, and the combination of LVI and TNM system enhanced the prognosis predictive accuracy. After confirmation, node-negative patients with LVI might be considered to be upstaged in pathological staging.