Claudin 18.2: An attractive marker in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive tumor with limited treatment options. Zolbetuximab, a monoclonal antibody against the tight junction protein Claudin 18.2 has recently been developed. At present, few and conflicting data have been reported regarding the clinical-pathological features of Claudin 18.2 expression in PDA. The present study investigated the expression of Claudin 18.2 in histological samples from PDA patients with the aim of verifying its utility as a therapeutic biomarker. Claudin 18.2 immunoreactivity was assessed by immunohistochemical staining on 70 formalin-fixed, paraffin-embedded PDA specimens (28 surgical specimens and 42 fine needle aspiration biopsies). The results obtained were associated with the clinicopathological characteristics and the survival rate of patients. Claudin 18.2 was detected only in neoplastic cells, not in normal pancreatic tissue. Claudin 18.2 was positive in 50% of samples and a higher expression was associated with well- and moderately-differentiated tumors and lymph node-negative status. The high expression of Claudin 18.2 in neoplastic tissue and absence in normal cells suggested that this protein had an attractive role in PDA as both a diagnostic and a prognostic-therapeutic marker. High expression of Claudin 18.2 in neoplastic tissue was associated with more favorable prognostic parameters and the high percentage of positive samples obtained suggests that Zolbetuximab may be suitable for a large number of patients.

Keywords: Claudin 18.2; immunohistochemistry; pancreatic ductal adenocarcinoma; tight junction; zolbetuximab.

Figure 1.

Immunohistochemical expression of CLDN18.2 in PDA samples. Examples of CLDN18.2 positive PDA with (A) 0/none, (B) 1+/weak (red arrow indicates a Claudin positive neoplastic gland with 1+ of staining intensity), (C) 2+/intermediate and (D) 3+/strong staining intensity. The yellow arrow indicates a normal negative pancreatic duct. Scale bar, 100 µm. PDA, pancreatic ductal adenocarcinoma; CLDN18.2, Claudin 18.2.

Figure 2.

Membranous Claudin 18.2-positive immunostaining in pancreatic ductal adenocarcinoma with 3+/strong staining intensity from a fine needle aspiration biopsy (magnification, ×10).

Figure 3.

Membranous Claudin 18.2-positive immunostaining in pancreatic ductal adenocarcinoma with 3+/strong staining intensity from a surgical specimen (magnification, ×20).

Figure 4.

Overall survival in patients with pancreatic ductal adenocarcinoma according to CLDN18.2 expression. CLDN18.2, Claudin 18.2.