Microenvironment and Biomarkers in Esophageal Cancers: An Approach for Early Detection and Identification

Q: What is the main goal of this study on esophageal cancers?

To investigate histological biomarkers that enable early and accurate identification of EAC-related changes, particularly in patients with GERD.

Q: How were the biomarkers evaluated in the cross-sectional study?

Immunohistochemistry was used to examine the P63 marker, and Masson’s trichrome staining was used to evaluate cancer progression and microenvironmental alterations.

Q: What did the results show regarding the P63 marker?

Most analyzed EAC-related cases were P63-negative, supporting non-squamous origins, while a subset of SCC control cases showed P63 positivity with a highly significant association.

Sep 21, 2026

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Esophageal cancer is a lethal malignancy with two major subtypes, ESCC and EAC, whose diagnosis—especially for tumors in the lower esophagus—can be error-prone, as EAC may be mistaken for ESCC. This cross-sectional study evaluates archival lower-esophageal histological samples using immunohistochemistry for the P63 marker and Masson’s trichrome staining to assess microenvironmental changes. Among 104 cases, P63 staining patterns and stromal collagen infiltration support distinguishing EAC-related alterations and suggest biomarkers for earlier identification, particularly in patients with GERD.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

Background and risk factors

Review began 11/05/2024 Review ended 11/18/2024 Published 11/22/2024 © Copyright 2024 Eltahir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. DOI: 10.7759/cureus.74242 Open Access Original Article Microenvironment and Biomarkers in Esophageal Cancers: An Approach for Early Detection and Identification Zakaria Eltahir 1, Gareth J. Jenkins 2, Alaa A. Eisa 3 , Mohamed H. Keayta 1, YousifA. Aljhani 1 , Omar Alfaroqui 4, 5 1. College of Applied Medical Sciences, Department of Clinical Laboratory Sciences, Taibah University, Medina, SAU 2. College of Medicine, Translation Clinical Trials Unit, Taibah University, Medina, SAU 3. Department of Pathology and Laboratory Medicine, Taibah University, Medina, SAU 4. Department of Histopathology, King Fahad Hospital, Medina, SAU 5. School of Medicine, Swansea University, Swansea, GBR Corresponding author: Zakaria Eltahir, [szak@hotmail.co.uk](szak@hotmail.co.uk) Abstract Background Esophageal cancer is a prevalent and highly lethal malignancy worldwide, comprising two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) . While both subtypes are frequently encountered, ESCC has historically been more common globally. However, in recent decades, EAC has emerged as the predominant type in industrialized nations, often developing from Barrett’s esophagus, a condition driven by chronic gastroesophageal reflux disease (GERD) . ESCC typically occurs in the upper esophagus, whereas EAC arises near the lower gastroesophageal junction. The etiology of esophageal cancer is multifactorial, with diverse causes and clinical management strategies. Notably, diagnosing tumors located in the lower esophagus presents significant challenges. EAC is particularly prone to diagnostic errors, as it can be mistaken for ESCC. This study aims to investigate potential histological biomarkers for EAC to facilitate early and accurate identification of histological changes, especially inpatients with GERD. Methods This cross-sectional study examined archival histological samples from patients with lower esophageal abnormalities. Immunohistochemistry was used to investigate the P63 marker, while Masson’s trichrome stain was employed to evaluate cancer progression and associated microenvironmental changes. Results A total of 104 cases were analyzed, including 13 with known P63-positive staining and five P63-negative controls. The remaining cases consisted of both precancerous and cancerous tissues diagnosed as EAC. Among these, 86 cases showed negative P63 staining, confirming their origin from non-squamous cells and supporting their classification as true Barrett’s-related epithelium. In contrast, five of the 13 SCC control cases exhibited P63 positivity, demonstrating a highly significant association (p < 0 .00001) . Additionally, Masson’s trichrome staining revealed stromal collagen fibers infiltrating the malignant tissue areas. Conclusions This study highlights the significance of the P63 marker in distinguishing between ESCC and EAC. It also suggests a potential role for Masson’s trichrome stain in identifying early microenvironmental changes associated with EAC progression. Categories: Gastroenterology, Pathology, Oncology Keywords: esophagus adenocarcinoma, esophagus cancers, masson trichrome, p63, tumor microenvironment Introduction Esophageal adenocarcinoma (EAC) is a malignancy primarily affecting the distal esophagus and the gastroesophageal junction (GEJ) . It is defined as a tumor with its epicenter located within 5 cm of the lower esophagus or the gastric side of the GEJ. This aggressive cancer ranks 11th in global cancer-related mortality [1] . Despite advancements in neoadjuvant chemotherapy and radiotherapy, the

FAQs

What is the main goal of this study on esophageal cancers?

To investigate histological biomarkers that enable early and accurate identification of EAC-related changes, particularly in patients with GERD.

How were the biomarkers evaluated in the cross-sectional study?

Immunohistochemistry was used to examine the P63 marker, and Masson’s trichrome staining was used to evaluate cancer progression and microenvironmental alterations.

What did the results show regarding the P63 marker?

Most analyzed EAC-related cases were P63-negative, supporting non-squamous origins, while a subset of SCC control cases showed P63 positivity with a highly significant association.

Sep 21, 2026

Uploaded by Clementine