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Int J Clin Exp Pathol 2013;6(11):2476-2486

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

Sabrina C Sopha, Purva Gopal, Nipun B Merchant, Frank L Revetta, David V Gold, Kay Washington, Chanjuan Shi

Department of Pathology, Microbiology and Immunology, Department of Surgery, Surgical Oncology, Vanderbilt University Medical Center,
Nashville, TN, USA; Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ, USA

Received September 1, 2013; Accepted October 3, 2013; Epub October 15, 2013; Published November 1, 2013

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. (IJCEP1309006).

Keywords: Pancreatic ductal adenocarcinoma, duodenal mucosal invasion, immunohistochemistry

Address correspondence to: Dr. Chanjuan Shi, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center,
1161 21st Avenue South, C-3321 MCN, Nashville, TN 37232, USA. Tel: 615-936-8342; Fax: 615-343-7023; E-mail: