The Role of SMAD4 as part of Immunohistochemical Panel to Differentiate Pancreatic Adenocarcinoma and Ampullary Adenocarcinoma and to Predict a More Aggressive Histopathological Prognostic Factors

Abstract

Background

Differentiating pancreatic ductal adenocarcinoma (PDAC) from ampullary adenocarcinoma is difficult. The treatment and prognosis are different. It is very important to determine the tumor's origin. Immunohistochemical examination, such as CK7 and MUC1, shows overlapping results. Loss of SMAD4 was higher in PDAC, so SMAD4 is thought to be one of the immunohistochemical panels. There are studies on poorer survival in cases with loss of SMAD4 and the association of histopathological prognostic factors with survival, so this study also assesses whether there is a relationship between loss of SMAD4 and histopathological prognostic factors.

Methods

Observational analytical study, cross sectional, total sampling, resection specimens of PDAC and ampullary adenocarcinoma, period January 2013 to December 2021. Ampullary adenocarcinoma with a pancreatobilliary subtype was excluded. Immunohistochemical examination using the SMAD4 primary antibody.

Results

Loss of SMAD4 was found in 12 cases (60%) of PDAC and 8 cases (44.4%) of ampullary adenocarcinoma including 2 cases of intestinal subtype, 3 cases of mixed intestinal-PB subtype and 3 cases of mixed PB-intestinal. Loss of SMAD4 with pT3/pT4 staging was found in 10 cases of PDAC and 7 cases of ampullary adenocarcinoma.

Conclusion

There was no significant relationship between loss of SMAD4 in PDAC and ampullary adenocarcinoma (p = 0.338). PDAC, on the other hand, had a higher SMAD4 loss than ampullary adenocarcinoma of intestinal subtype or mixed type of intestinal dominance. Pathological staging of pT was found to be significantly higher in cases of loss of SMAD4 in ampullary adenocarcinomas and showed a higher trend in PDAC.