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


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.


CONCLUSIONS
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.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center Nashville, TN, USA.
Sabrina C
SC
Sopha
Purva
P
Gopal
Nipun B
NB
Merchant
Frank L
FL
Revetta
David V
DV
Gold
Kay
K
Washington
Chanjuan
C
Shi
D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D004386:Duodenum / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011237:Predictive Value of Tests; D011379:Prognosis
D014408:Biomarkers, Tumor
Pancreatic ductal adenocarcinoma; duodenal mucosal invasion; immunohistochemistry