Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

Cancer Biol Med. 2024 Jan 3;21(5):416-432. doi: 10.20892/j.issn.2095-3941.2023.0363.

Abstract

Objective: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain.

Methods: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated.

Results: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-node-metastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS.

Conclusions: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Keywords: Ki-67; Pancreatic ductal adenocarcinoma; TNM stage; differentiation; prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / mortality
  • Carcinoma, Pancreatic Ductal* / pathology
  • Carcinoma, Pancreatic Ductal* / surgery
  • Cell Differentiation
  • Female
  • Humans
  • Ki-67 Antigen* / analysis
  • Ki-67 Antigen* / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading*
  • Neoplasm Staging
  • Pancreatectomy
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Pancreatic Neoplasms* / surgery
  • Prognosis
  • Retrospective Studies

Substances

  • Ki-67 Antigen
  • Biomarkers, Tumor