Grading of tumor budding in intestinal-type early gastric adenocarcinoma and its role in assessing the risk of lymph node metastasis

Abstract

Objective: To investigate the role of tumor budding (TB) in predicting lymph node metastasis of intestinal-type early gastric adenocarcinoma, and to determine the optimal cutoff value of TB number. Methods: A total of 202 patients with intestinal-type early gastric adenocarcinoma, who underwent surgical operation at the Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu, China from 2008 to 2018 were included. According to the International Tumor Budding Consensus Conference (ITBCC) criteria, the number of TB for each case was assessed. The receiver operating characteristic (ROC) curve was employed to determine the optimal cutoff value of TB number for predicting lymph node metastasis, and multivariate logistic regression was used to analyze whether a high TB number was an independent risk factor for lymph node metastasis. In addition, in the patients, who met the indications for endoscopic resection and developed lymph node metastasis, the association of a high number of TB with lymph node metastasis was examined. Results: TBs were observed in 63.4% (128/202) of intestinal-type early gastric adenocarcinomas. Using ROC curve, 4 TBs was found as the optimal cutoff value to predict lymph node metastasis (area under the curve 0.767; sensitivity 0.657; specificity 0.780). Therefore, the 202 cases were divided into two groups: the high-budding (≥4 TBs) group (n=60) and the low-budding (<4 TBs) group (n=142). The high-budding group exhibited a higher rate of lymph node metastasis than that of the low-budding group (41.7% vs 9.1%, P<0.01), and ≥4 TBs was associated with deeper invasion and lymph vessel invasion (P<0.01). The multivariate regression model showed that ≥4 TBs was an independent risk factor for lymph node metastasis (Hazard ratio=8.760, 95%CI 2.648-28.987; P<0.01). Meanwhile, 4 TBs as the cutoff value could better predict lymph node metastasis than the cutoff value advised by the ITBCC. In addition, 3 cases were found to have developed lymph node metastasis even that they met the expanded indications for endoscopic resection, and 2 of these 3 cases exhibited a higher TB number (≥4 TBs). Conclusions: More than 4 TBs are a useful indicator for predicting lymph node metastasis in intestinal-type early gastric adenocarcinoma. It may be used to as an endoscopic resection criterion for patients with a high risk of lymph node metastasis.