The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment

Sep 24, 2026

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Linitis Plastica (LP) is a rare, aggressive gastric tumor with a distinctive infiltrative growth pattern that thickens gastric folds and produces a “leather bottle” appearance. Its extreme heterogeneity reflects mutations in oncogenic and tumor-suppressor genes, dysregulated molecular pathways, and alterations in stromal cells and tight-junction–related proteins. Defining the molecular basis of tumorigenesis and clarifying cancer–stroma interplay supports the discovery of diagnostic methods, biomarkers, and therapeutic targets. Surgery remains central as both palliative and curative management. This review consolidates recent molecular and clinical advances and evaluates novel management strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Molecular background of Linitis Plastica

Diagnostic challenges and biomarkers

Targeted/therapeutic approaches

Role of surgery in management

Review The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment Grigorios Christodoulidis 1,*, Konstantinos Eleftherios Koumarelas 1, Marina Nektaria Kouliou 1, Maria Samara 2, Eleni Thodou 2 and Dimitris Zacharoulis 1 Citation: Christodoulidis, G.; Koumarelas, K.E.; Kouliou, M.N.; Samara, M.; Thodou, E.; Zacharoulis, D. The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment. Int. J. Mol. Sci. 2023, 24, 14680. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms241914680](10.3390/ijms241914680) Academic Editor: Nam Deuk Kim Received: 27 August 2023 Revised: 20 September 2023 Accepted: 26 September 2023 Published: 28 September 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of General Surgery, University Hospital of Larissa, University of Thessaly, Biopolis Campus, 41110 Larissa, Greece; [kostaskoumarelas@gmail.com](kostaskoumarelas@gmail.com) (K.E.K.); [marinakouliou@gmail.com](marinakouliou@gmail.com) (M.N.K.); [zachadim@yahoo.com](zachadim@yahoo.com) (D.Z.) 2 Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis Campus, 41110 Larissa, Greece; [msamar@med.uth.gr](msamar@med.uth.gr) (M.S.); [ethodou@uth.gr](ethodou@uth.gr) (E.T.) * Correspondence: [xristodoulidis@uth.gr](xristodoulidis@uth.gr); Tel.: +30-69-72227992 Abstract: Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the inﬁltration of the gastric wall, the thickening of the gastric folds and a “leather bottle appearance”. LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management. Keywords: Linitis Plastica; Borrmann type IV; oncogenes in LP; biomarkers; targeting agents; surgery 1. Introduction Gastric cancer (GC) ranks as the ﬁfth most common malignancy worldwide, with approximately 1.1 million new cases annually. It stands out as having one of the highest mortality rates with the third most deaths [1–4] . Linitis Plastica (LP), a subtype of gastric cancer, constitutes 10% of all GC cases [2,5,6] . First observed in the 16th and 17th centuries, it was formally described in 1859 by William Brinton [7] . Macroscopically, LP is characterized by the thickening of the gastric folds due to accumulation of ﬁbrous tissue, often referred to as the “Leather-bottle stomach” [3,5,7,8] . The term “Linitis” derives from its“linen-like” macroscopical image. LP originates from the fundic gland cells and inﬁltrates the entire stomach with a desmoplastic growth pattern, unlike the development of a solid tumor. Tumor cells are dispersed within the thickened ﬁbrous tissue, extending into the submucosal and serous layer [5,7,9–11] . In 91.1% of cases, LP presents as a poorly differentiated adenocarcinoma, and in 77.7% of cases, it is often histologically linked with signet ring cells [8] . However, diagnosing LP is a complex and challenging endeavor, due to the i

FAQs

What defines the clinical and pathological development pattern of Linitis Plastica?

Linitis Plastica is characterized by infiltration of the gastric wall, thickening of the gastric folds, and a “leather bottle appearance,” reflecting a desmoplastic growth pattern rather than a solid tumor mass.

Why is LP considered highly heterogeneous at the molecular level?

LP heterogeneity stems from mutations in oncogenic and tumor suppressive genes and multiple molecular pathways, together with mutations in stromal cells and proteins associated with tight junctions.

How does surgery contribute to LP management?

Surgery plays a pivotal role, serving as both a palliative and a curative procedure depending on clinical context and resectability.

Sep 24, 2026

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