Diagnostic and therapeutic implications of a novel immunohistochemical panel detecting duodenal mucosal invasion by pancreatic ductal adenocarcinoma

Abstract

Background: We investigated a series of pancreaticoduodenectomy and duodenal biopsies with a panel of immunohistochemical markers to identify duodenal mucosal invasion by pancreatic ductal adenocarcinoma (PDAC), including markers of poor prognosis and targets of promising novel immunotherapies.

Materials and methods: Eighteen consecutive pancreaticoduodenectomy specimens with duodenal mucosal invasion by PDAC were examined for expression of MUC1, MUC4, MUC5AC, MUC6, mesothelin, MUC2, CDX2, and DPC4 on formalin-fixed, paraffin-embedded sections of duodenal-ampullary-pancreatic junctions. Expression of all but MUC6 was also assessed in duodenal biopsies from 12 patients with duodenal mucosal invasion by PDAC.

Results: The duodenal mucosa expressed MUC1 (crypts), MUC2 (goblet cells), MUC6 (Brunner glands), CDX2, and DPC4. PDACs in the duodenal mucosa from the resection (n=16-18) and biopsy (n=12) specimens were marked as follows: MUC1 100% (30/30), MUC4 83% (24/29), MUC5AC 83% (25/30), mesothelin 82% (23/28), MUC2 7% (2/30), and CDX2 36% (10/28). Loss of DPC4 expression was seen in 16 of 29 (55%) cases. Reactive mucosa adjacent to PDAC expressed MUC4, MUC5AC and mesothelin in 65% (17/26), 19% (5/27), and 19% (5/26) of cases, respectively. While MUC5AC and mesothelin had high diagnostic accuracy for detection of PDAC, MUC2, CDX2 and DPC4 expression demonstrated negative correlation with PDAC, with absent expression being highly specific for PDAC.

Conclusion: Immunohistochemical labeling for PDAC biomarkers may aid the diagnosis of PDAC in duodenal biopsy, especially in situations where diagnosis of a pancreatic mass is challenging.

Keywords: Pancreatic ductal adenocarcinoma; duodenal mucosal invasion; immunohistochemistry.

Figure 1

Duodenal mucosal involvement by pancreatic ductal adenocarcinoma (PDAC) in an epithelial colonization fashion (original magnification 200X). A. Hematoxylin and eosin stain showing duodenal epithelial cells replaced by malignant cells (Black arrows: malignant epithelium; Yellow arrows: normal epithelium); B. Diffuse strong MUC1 expression in PDAC; C. Diffuse MUC4 expression in PDAC; D. MUC5AC expression in PDAC; E. Diffuse mesothelin expression in PDAC; F. Lack of MUC2 expression in PDAC (Black arrows: malignant epithelium); G. No CDX2 expression in PDAC (Black arrows: malignant epithelium); H. Lack of DPC4 expression in PDAC (Black arrows: malignant epithelium).

Figure 2

Duodenal mucosal involvement by pancreatic ductal adenocarcinoma in a glandular infiltrating fashion (original magnification 100X). A. Hematoxylin and eosin stain showing malignant glands in the duodenal mucosa; B. Diffuse strong MUC1 expression in malignant glands; C. Diffuse strong expression of MUC4 in malignant glands; D. Focal strong MUC5AC expression in malignant glands (note: MUC5AC-positive mucin in the glands); E. Diffuse mesothelin expression in malignant glands; F. Lack of MUC2 expression in malignant glands; G. No CDX2 expression in malignant glands; H. Loss of DPC4 in malignant glands.

Figure 3

Duodenal mucosal involvement by pancreatic ductal adenocarcinoma (PDAC) in one duodenal biopsy. A. Hematoxylin and eosin stain showing malignant glands in the duodenal biopsy (original magnification 100X; black arrows: malignant glands); B. Diffuse strong MUC1 expression in malignant glands (100X); C. MUC4 expression in malignant glands (100X; note: scattered MUC4 expression in background duodenal mucosa); D. MUC5AC expression in malignant glands (200X; note: MUC5AC positive mucin in the glands); E. Focal mesothelin expression by malignant glands (200X); F. Lack of MUC2 expression in one large malignant glands (200X); G. No CDX2 expression in malignant glands (200X); H. Loss of DPC4 expression in malignant glands (200X).