Detection of Duodenal Mucosal Invasion by Pancreatic Ductal Adenocarcinoma: A Novel Immunopanel with Prognostic and Therapeutic Implications
Sabrina C Wentz, Purva Gopal, Nipun B Merchant, Frank L Revetta, David V Gold, M Kay Washington, Chanjuan Shi. Vanderbilt University Medical Center, Nashville, TN; Garden State Cancer Center, Belleville, NJ
Background: Identification of duodenal mucosal invasion by pancreatic ductal adenocarcinoma (DMI-PDAC) is a diagnostic challenge on biopsy specimens. Despite their aggressiveness, well-differentiated PDACs are morphologically indistinct from normal or reactive duodenal/ampullary epithelium. We investigated a series of pancreaticoduodenectomy specimens with an immunopanel to identify DMI-PDAC, including markers of poor prognosis and targets of promising novel immunotherapies. This panel may increase the sensitivity of detection, thus accelerating the curative resection timeline and increasing surgical eligibility, while offering theranostic information.
Design: Seventeen consecutive pancreaticoduodenectomy specimens with DMI-PDAC and one control case of PDAC without invasion were included. Immunohistochemical labeling for MUC1 (VU4H5), MUC1 (MA5), MUC2, MUC4 (8G7), MUC5AC, MUC6, PAM4, DPC4, CDX2, and mesothelin were performed on formalin-fixed, paraffin-embedded sections of duodenal-ampullary-pancreatic junctions. Staining patterns of DMI-PDAC were independently recorded by three pathologists (SCW, GP, CS).
Results: Normal/reactive duodenal and ampullary mucosa were MUC1+/MUC2+/MUC4-/MUC5AC-/MUC6-/MA5-/PAM4-/DPC4+/CDX2+/Meso- and MUC1+/MUC2+/MUC4-/MUC5AC-/MUC6+/MA5+/PAM4-/DPC4+/CDX2-/Meso-, respectively. In general, PDACs stained MUC1+/MUC2-/MUC4+/MUC5AC+/MUC6-/MA5+/PAM4+/DPC4-/CDX2-/Meso+. In DMI-PDACs, MUC1 (VU4H5) labeling was strong and uniform regardless of differentiation (18/18, 100%). DMI-PDACs were also labeled with MUC5AC (17/18, 94.4%), mesothelin (15/18, 83.3%), and PAM4 (13/18, 72.2%). MUC2, DPC4, and CDX2 were not expressed in 94.4% (17/18), 55.6% (10/18), and 72.2% (13/18) of the PDAC, respectively. A tumor subset expressing DPC4 and/or CDX2 was differentiated from duodenal or ampullary mucosa with mesothelin. DMI-PDACs also labeled with MUC6 (7/18, 38.8%) and showed increased MUC4 and MUC1 (MA5) labeling with de-differentiation (13/18, 72.2% and 16/18, 88.9%).
Conclusions: An abbreviated panel of MUC1 (VU4H5), MUC4, MUC5AC, mesothelin, PAM4, CDX2 and DPC4 consistently highlights DMI-PDAC. Although MUC1 and MUC5AC are sensitive markers of DMI-PDAC, expression of mesothelin and PAM4 and loss of DPC4 and CDX2 expression are more specific for DMI-PDAC. MUC4 and MUC1 expression are known to associate with higher grade and poor prognosis. Cases expressing PAM4, mesothelin, or MUC1 may be eligible for promising novel immunotherapies.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 76, Wednesday Morning