Tumor Budding and Other Risk Factors of Lymph Node Metastasis in Submucosal Early Gastric Carcinoma

Abstract

Compared with early gastric intramucosal carcinoma, submucosal carcinoma is known to have a higher risk for lymph node metastasis (LMN), but risk factors in submucosal carcinoma remain elusive. In this multicenter study with 621 radical gastrectomies for submucosal early gastric carcinoma, we investigated tumor budding and other risk factors of LMN that were identified in 172 cases (27.7%). Overall, independent high-risk factors for LMN included lymphovascular invasion (odds ratio, 3.9; 95% confidence interval, 2.5-6.1), tumor budding (odds ratio, 3.3; 95% confidence interval, 1.9-5.9), mixed tubular/papillary adenocarcinoma with poorly cohesive carcinoma (odds ratio, 2.1; 95% confidence interval, 1.0-4.3), and female sex (odds ratio, 1.6; 95% confidence interval, 1.0-2.6), whereas gastric cardiac submucosal carcinomas had a significantly lower risk for LMN (odds ratio, 0.5; 95% confidence interval, 0.3-0.9). In 276 well/moderately differentiated tubular or papillary submucosal early gastric carcinomas, independent risk factors were tumor budding (odds ratio, 3.7; 95% confidence interval, 1.6-8.7), deep submucosal (SM2) invasion (odds ratio, 3.1; 95% confidence interval, 1.3-7.6), and lymphovascular invasion (odds ratio, 2.7; 95% confidence interval, 1.3-5.6). In 174 cases without tumor budding and lymphovascular invasion, no LMN was identified in 47 cardiac tumors, and 15 tumors <1.0 cm in size. In conclusion, tumor budding, lymphovascular invasion, mixed tubular/papillary adenocarcinoma with poorly cohesive carcinoma, and female gender were found to be significant high-risk factors for LMN in submucosal early gastric carcinoma, while submucosal gastric cardiac carcinoma had a significantly lower risk for nodal metastasis.

Adenocarcinoma with mixed subtypes in the early and advanced gastric cancer.

“…Our study proved that there were no differences in the aggressive tumor features, such as N stage, M stage, and tumor size between AM and other three histologic subtypes in EGC, which is not consistent with previous researches [9]. We think this is due to the fact that the comparison is not just with adenocarcinoma in the research mentioned above.…”

“…There were some researches on the prognosis of GC patients with AM [8,9]. However, there is no report on the comparison of prognosis among AM, classic adenocarcinoma (CA), MAC and SRCC in EGC and AGC, respectively.…”

Tumour budding and its clinical implications in gastrointestinal cancers

“…These results were confirmed in a subgroup analysis of intestinal-type cancers but not in diffuse-type adenocarcinoma. 76 In their evaluation of tumour budding in 621 radical gastrectomies for submucosal early gastric carcinoma, 77 Du et al identified high-grade tumour budding as a predictor of lymph node metastases (OR 3.3, 95% CI 1.9–5.9). Moreover, when Ulase et al applied the ITBCC tumour-budding score to 456 surgically resected gastric cancers, they found that the BD score was significantly associated with sex, Laurén phenotype, pT-, pN- and pM classification, as well as perineural invasion and survival times.…”

Modified Tumor Budding as a Better Predictor of Lymph Node Metastasis in Early Gastric Cancer: Possible Real-World Applications

“…Tumor budding (TB) is a well-known risk factor for LNM in early-stage colorectal cancer [ 10 , 11 , 12 , 13 ]. Recently, it has also emerged as a potential predictor of LNM in gastric cancer (GC) [ 12 , 14 , 15 , 16 , 17 , 18 , 19 ]. However, studies on the association between TB and LNM in GC have been conducted mainly in intestinal-type carcinoma [ 12 , 14 , 19 ], as it is difficult to discern TB in poorly cohesive carcinoma (PCC) cases because of its discohesive pattern [ 16 , 20 ].…”