"Paneth cell differentiation associated with neoadjuvant therapy in eso" by Madhurya Ramineni, Sarah K. Findeis et al.
 

Paneth cell differentiation associated with neoadjuvant therapy in esophageal adenocarcinoma

Department

Pathology

Document Type

Article

Publication Title

American Journal of Clinical Pathology

Abstract

Objectives: Paneth cells and Paneth cell metaplasia are well-known in pathology as foundational components in the gastrointestinal system. When within malignant cells (Paneth cell differentiation [PCD]), however, the function and significance of these cells is less well understood. Here, we present findings from the first study focused on PCD in postneoadjuvant esophageal adenocarcinoma (EAC) resection specimens.

Methods: Patients with EAC treated with neoadjuvant chemoradioation and followed by esophagectomy between 2012 and 2018 in our institution were retrospectively evaluated. A tissue microarray was constructed, and special and immunohistochemical stains were performed.

Results: A total of 64 cases were collected, of which 8 had PCD, as highlighted by periodic acid-Schiff with diastase staining. Adenocarcinomas with PCD were more commonly seen in patients 60 to 70 years of age and typically had a poorly differentiated morphology, observationally fewer stromal mucinous changes, and less lymph node metastasis. β-catenin activation induced by neoadjuvant therapy was more frequent in the PCD-positive cases. Patients with PCD-positive disease had low programmed cell death 1 ligand 1 levels, no positive or equivocal ERBB2 (HER2) expression, and low CD8-positive T-cell infiltration; they were also mismatch repair proficient. Patients with PCD-positive disease showed a survival pattern inferior to that of patients with PCD-negative disease.

Conclusions: When induced by neoadjuvant therapy in EAC, PCD is associated with high β-catenin activation, less expression of targetable biomarkers, and a potentially worse clinical prognosis.

Keywords: CD8+ T cell; PD-L1; Paneth cell differentiation; esophageal adenocarcinoma; neoadjuvant therapy; survival; β-catenin.

First Page

87

Last Page

96

DOI

10.1093/ajcp/aqae098

Volume

163

Issue

1

Publication Date

1-28-2025

Medical Subject Headings

Humans; Neoadjuvant Therapy; Esophageal Neoplasms (pathology, therapy, metabolism); Male; Middle Aged; Adenocarcinoma (pathology, therapy, metabolism); Female; Aged; Paneth Cells (pathology, metabolism); Retrospective Studies; Cell Differentiation; Esophagectomy; Adult; Biomarkers, Tumor (metabolism)

PubMed ID

39110451

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