title: Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.
abstract: OBJECTIVE
  Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.
  
  
  METHODS
  Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS) was statistically analyzed.
  
  
  RESULTS
  Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145) of them. Single cell invasion and large cell invasion were observed in 62.8% (186) and 16.9% (50) of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260,P<0.001). Similarly, the OS of patients with single cell invasion and large cell invasion was reduced (single cell invasion, HR: 3.553,P<0.001; large cell invasion, HR: 2.466,P<0.001). Following multivariate analysis, tumor budding and single cell invasion were observed to be independent risk factors for gastric adenocarcinoma (P<0.05). According to the Lauren classification, patients with intestinal-type adenocarcinoma had better outcomes than those with diffuse-type adenocarcinoma (HR: 2.563,P<0.001).
  
  
  CONCLUSIONS
  Tumor budding and single cell invasion in gastric adenocarcinoma are associated with an unfavorable prognosis.
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan.
authors.forename: Keying
authors.initials: K
authors.lastname: Che
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan.
authors.forename: Xiao
authors.initials: X
authors.lastname: Qu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University.
authors.forename: Tiehong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan; Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Shen
keywords: gastric carcinoma; invasion type; metastasis; pathology; prognosis