Clinicopathological, immunohistochemical, and overall-survival associations of poorly cohesive gastric carcinoma stratified by signet ring cell percentage

doi:10.5306/wjco.125097

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World Journal of Clinical Oncology

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2218-4333

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Clin Oncol. Oct 24, 2026; 17(10): 125097
Published online Oct 24, 2026. doi: 10.5306/wjco.125097

Clinicopathological, immunohistochemical, and overall-survival associations of poorly cohesive gastric carcinoma stratified by signet ring cell percentage

Yi-Han Zheng, Yang-Yang Wang, Shu-Chang Wang, Chao-Jie Wang, Yan-Ying Shen, Jian-Zhi Cui, Shi-Meng Liu, Ye-Hao Zhang, Xue-Qin Zeng, En-Hao Zhao

Yi-Han Zheng, Yang-Yang Wang, Shu-Chang Wang, Chao-Jie Wang, Jian-Zhi Cui, Shi-Meng Liu, Ye-Hao Zhang, En-Hao Zhao, Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

Yan-Ying Shen, Xue-Qin Zeng, Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

Co-first authors: Yi-Han Zheng and Yang-Yang Wang.

Co-corresponding authors: Xue-Qin Zeng and En-Hao Zhao.

Author contributions: Zheng YH and Wang YY contributed to the manuscript writing; Zheng YH, Wang SC, and Wang CJ contributed to the statistical analysis; Zeng XQ and Shen YY contributed to the pathological study; Zheng YH, Cui JZ, Liu SM, and Zhang YH contributed to the follow-up of the patients and the data collection; Zeng XQ contributed to the basis for pathological grouping; Zeng XQ and Zhao EH contributed to the critical revision of the manuscript; Zhao EH contributed to the supervision and organization of the study. Zeng XQ and Zhao EH contributed equally to this work as co-corresponding authors. Zheng YH and Wang YY contributed equally to this work as co-first authors.

AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.

Supported by the Natural Science Foundation of Shanghai Municipality, No. 23ZR1439400 to Zhao EH; the National Natural Science Foundation of China, No. 82103348 to Wang YY; and the Fundamental Research Funds for the Central Universities, No. YG2023QNA10 to Wang SC.

Institutional review board statement: This retrospective observational study was conducted in accordance with the ethical principles of the Declaration of Helsinki. The study was approved by the Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine (Ethics Approval No. LY2022-091-B).

Informed consent statement: The Ethics Committee waived the requirement for informed consent due to the study's retrospective nature and the use of anonymized data.

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: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Corresponding author: En-Hao Zhao, MD, PhD, Chief Physician, Professor, Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Shanghai 200127, China. zhaoenhao@renji.com

Received: July 1, 2026
Revised: August 24, 2026
Accepted: October 16, 2026
Published online: October 24, 2026
Processing time: 115 Days and 14.6 Hours

Abstract

BACKGROUND

Poorly cohesive carcinoma (PCC) is a major histological type of gastric cancer characterized by decreased intercellular adhesion and manifests as isolated tumor cells or small, scattered clusters. PCC is morphologically heterogeneous and comprises two pathological components: Signet ring cell carcinoma (SRC) and PCC-not otherwise specified (PCC-NOS). According to the European Consensus, PCC is further classified into three subtypes based on the SRC proportion: SRC (≥ 90%), SRC/PCC-NOS (10% < SRC < 90%), and PCC-NOS (≤ 10%).

AIM

To comprehensively evaluate the clinicopathological, immunohistochemical, and prognostic profiles of PCC and its subtypes stratified by SRC proportion.

METHODS

This single-center retrospective cohort study included 1592 patients who underwent gastrectomy for gastric cancer between September 2016 and December 2018, with a loss-to-follow-up rate of 23.6%. Among them, 374 patients were diagnosed with PCC (70 SRC, 171 SRC/PCC-NOS, and 133 PCC-NOS) and 1218 had non-PCC carcinoma. Propensity score matching (PSM) was performed to minimize selection bias between the PCC and non-PCC groups and among the PCC subtypes. Survival outcomes, clinicopathological features, and immunohistochemical markers were analyzed.

RESULTS

Five-year overall survival (OS) did not differ significantly between the non-PCC and PCC groups (68.87% vs 69.11%, P = 0.4425), and this finding remained consistent after PSM (P = 0.9189). Among the PCC subtypes, the SRC group presented at an earlier tumor stage. Unadjusted 5-year OS was highest in the SRC group (80.77%), followed by the PCC-NOS (67.80%) and SRC/PCC-NOS (65.03%) groups (P = 0.0460). However, this survival advantage was no longer significant after PSM (P = 0.5820). Immunohistochemical analysis revealed inter-subtype heterogeneity in the expression of Ki67, mismatch repair (MMR) proteins, and programmed death protein ligand 1 (PD-L1). PD-L1 expression tended to be lower in the SRC group, whereas all cases with MMR protein loss were PCC-NOS, while the result remains exploratory and descriptive with the limitation of sample size.

CONCLUSION

This study demonstrated that PCC as a whole had a prognosis comparable to that of other gastric cancers. However, PCC subtypes exhibited distinct clinicopathological and immunohistochemical profiles, with SRC associated with an earlier stage and a better OS. These findings support the clinical relevance of PCC subclassification and warrant further validation in larger cohorts.

Keywords: Gastric adenocarcinoma; Poorly cohesive carcinoma; Signet ring cell carcinoma; Pathological classification; Prognosis; Retrospective cohort study

Core Tip: This single-center retrospective cohort study evaluated poorly cohesive gastric carcinoma and its subtypes, defined by the proportions of signet ring cell (SRC) and poorly cohesive carcinoma-not otherwise specified (PCC-NOS) components, and identified distinct clinicopathological and immunohistochemical profiles. Although the SRC-dominant group was associated with superior overall survival, this prognostic advantage disappeared after propensity score matching, whereas the PCC-NOS-dominant group was potentially associated with microsatellite instability and programmed death protein ligand 1 expression. These findings emphasize the need for further investigation and comprehensive evaluation of poorly cohesive carcinoma and its subtypes.