Comprehensive immunohistochemical analysis associated with the tumor microenvironment including monocarboxylate transporters in pancreatic ductal adenocarcinoma.

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma is an aggressive neoplasm with poor prognosis. The metabolic properties of its desmoplastic stroma are hypothesized to contribute to disease progression. Aberrant metabolism in tumor cells and desmoplastic stroma results in the accumulation of metabolic by-products, with lactate being the most important, released into the extracellular space by monocarboxylate transporters (MCTs). This study aimed to determine the prognostic value of these markers and identify potential therapeutic targets.

STUDY DESIGN/MATERIALS AND METHODS: Eighty-eight patients with Pancreatic adenocarcinomas (PDAC) were included. The tumoral and/or stromal expression of MCT1 , MCT4 , SMAD4 , vimentin, Ki67 , CD10 , and smooth muscle actin were investigated using the immunohistochemical analysis.

RESULTS/CONCLUSIONS: High MCT1 expression in tumor tissue was an independent prognostic marker for overall survival ( P < 0.01). Intense MCT1 expression in tumor tissue was associated with larger tumor size ( P < 0.05). Vimentin positivity and a higher Ki67 proliferation index were observed in the patients with lymphovascular invasion ( P < 0.05 and, P < 0.01, respectively). SMAD4 loss was higher in patients with metastasis ( P < 0.05). The overall survival was significantly reduced when the Ki67 proliferation index exceeded 50% ( P < 0.01). In conclusion, overexpression of MCT1 , a high Ki67 proliferation index, and loss of SMAD4 expression may serve as prognostic indicators of poor outcomes in PDAC. These findings hold the potential to guide the development of more effective therapeutic strategies for treating PDAC.