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

A Multicenter Clinicopathologic Study in 621 Radical Gastrectomies of Chinese Patients

Du, Mingzhan MD, PhD*; Chen, Ling MD, MS; Cheng, Yuqing MD, MS; Wang, Yaohui MD, MS§; Fan, Xiangshan MD, PhD; Zhang, Yifen MD, PhD§; Zhou, Xiaoli MD, PhD; Guo, Lingchuan MD, PhD*; Xu, Guifang MD, PhD; Zou, Xiaoping MD, PhD; Huang, Qin MD, PhD†,¶

The American Journal of Surgical Pathology: May 13, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/PAS.0000000000001276
Original Article: PDF Only
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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.

*Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou

Department of Pathology, the Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School

§Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine

Department of Gastroenterology, the Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing

Department of Pathology, the Changzhou Second Hospital affiliated to Nanjing Medical University, Changzhou, China

Department of Pathology and Laboratory Medicine, VA Boston Healthcare System, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA

M.D., L.C., Y.C., and Y.W. contributed equally.

Conflicts of Interest and Source of Funding: The study was financially supported in part by Jiangsu province’s key clinical specialist fund (NO:5201011305000606) and by grants from the Science and Technology Development Project of the Nanjing City (ZKX05013, ZKX07011) in Nanjing, China. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Qin Huang, MD, PhD, Department of Pathology and Laboratory Medicine, VA Boston Healthcare System, Harvard Medical School and Brigham and Women’s Hospital, 1400 VFW Parkway, West Roxbury, MA 02132 (e-mail: qinhuang0122@gmail.com).

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