title: High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk.
abstract: OBJECTIVE
  This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk.
  
  
  METHODS
  The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis.
  
  
  RESULTS
  Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria.
  
  
  CONCLUSIONS
  Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification.
authors.affiliation: Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Bangxing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000379:methods; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy