Retrospective Cohort Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2025; 17(6): 107021
Published online Jun 15, 2025. doi: 10.4251/wjgo.v17.i6.107021
Evaluation of tumor budding, desmoplastic reaction, and lymphocytic infiltration in predicting survival for pancreatic ductal adenocarcinoma
Anıl Alpsoy, Aysen Yavuz, Kubra Simsek, Busra Altunay, Mustafa Karaca, Betul Unal, Cumhur I Bassorgun, Ali M Tatli, Gulsum O Elpek
Anıl Alpsoy, Afyonkarahisar State Hospital, Afyonkarahisar 03000, Türkiye
Aysen Yavuz, Kubra Simsek, Cumhur I Bassorgun, Gulsum O Elpek, Department of Pathology, Akdeniz University, School of Medicine, Antalya 07070, Türkiye
Busra Altunay, Kütahya City Hospital, Kütahya 43000, Türkiye
Mustafa Karaca, Department of Internal Medicine, Akdeniz University, Antalya 07070, Türkiye
Betul Unal, Antalya Bilim University, Antalya 07070, Türkiye
Ali M Tatli, Department of Oncology, Akdeniz University, School of Medicine, Antalya 07070, Türkiye
Author contributions: Alpsoy A and Elpek GO designed and performed the research and wrote the paper; Yavuz A, Simsek K, Altunay B, Unal B, and Bassorgun CI were involved in the data curation, investigation, and resources; Tatli AM and Karaca M provided clinical advice; All authors equally contributed to the analysis of the data, and read and approved the final manuscript.
Institutional review board statement: This study was conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Akdeniz University Clinical Research Ethics Committee (Approval Number: KAEK-915, Date: December 13, 2023).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous data obtained after each patient agreed to treatment and data sharing by written permission.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Gulsum O Elpek, MD, Professor, Department of Pathology, Akdeniz University, School of Medicine, Dumlupinar Bulvarı, Antalya 07070, Türkiye. elpek@akdeniz.edu.tr
Received: March 14, 2025
Revised: April 15, 2025
Accepted: May 19, 2025
Published online: June 15, 2025
Processing time: 92 Days and 5.7 Hours
Abstract
BACKGROUND

Although previous findings indicated that pathological assessment of tumor budding (TB), desmoplastic reaction (DR), and tumor-infiltrating lymphocytes (TILs) may play a role in determining tumor behavior in many malignancies, the relationship between TB, DR, and TILs in patients with pancreatic ductal adenocarcinoma (PDAC) is still unknown.

AIM

To evaluate relationships of TB, DR, and TILs with histopathological parameters and determine their prognostic value in patients with PDAC.

METHODS

The study cohort comprised 100 patients diagnosed with PDAC. Peritumoral budding (PTB) and intratumoral budding (ITB) were assessed according to the International Tumor Budding Consensus Conference guidelines. DR was classified based on stromal maturation. TILs were evaluated semiquantitatively with a 5% cutoff. Additionally, cases were categorized into two groups according to lymphocyte density: No/Low lymphocytes and medium/high lymphocytes.

RESULTS

A significant correlation was observed between ITB and PTB (r = 0.890). Higher PTB was associated with fewer TILs and immature stroma (P < 0.001). PTB and TILs were significantly related to tumor dimension, lymphovascular invasion, lymph node metastasis (LNM), and stage (P < 0.005). ITB was also associated with the presence of lymph node involvement. The results of the univariate analysis revealed a significant correlation between poor survival rates and the presence of lymphovascular invasion, LNM, PTB, ITB, and TILs according to scoring (P < 0.001). The multivariate analysis revealed LNM, PTB, ITB, and TILs according to scoring as independent prognostic factors.

CONCLUSION

TB assessment stratified patients with PDAC. PTB-ITB correlation showed diagnostic relevance of ITB in biopsy specimens. The prognostic significance of DR and interplay with TIL subsets warrant further investigation.

Keywords: Pancreatic ductal adenocarcinoma; Tumor microenvironment; Tumor budding; Desmoplastic reaction; Tumor-infiltrating lymphocytes; Prognostic factors

Core Tip: Pancreatic ductal adenocarcinoma is a highly aggressive malignancy, necessitating novel histopathological markers for better prognostic stratification. This study evaluated tumor budding, desmoplastic reaction, and tumor-infiltrating lymphocytes in patients with pancreatic ductal adenocarcinoma. Peritumoral budding (PTB) correlated with tumor size, while intratumoral budding (ITB) was linked to lymph node involvement. Both PTB and ITB were independent prognostic factors for poor survival. Additionally, high PTB and ITB levels were associated with immature stroma, suggesting a role in epithelial-mesenchymal transition. These findings highlighted the prognostic value of tumor budding and its potential integration into pathology reporting protocols.