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Non-ampullary duodenal adenocarcinoma (DAC) is a rare malignancy. Little information is available concerning the histopathological prognostic factors associated with DAC. Carbonic anhydrases (CAs) are metalloenzymes catalyzing the universal reaction of CO 2 hydration. Isozymes CAII, CAIX, and CAXII are associated with prognosis in various cancers. Our aim was to analyze the immunohistochemical expressions of CAII, CAIX, and CAXII in normal duodenal epithelium, duodenal adenomas, and adenocarcinoma and their associations with clinicopathological variables and survival. Our retrospective study included all 27 DACs treated in Oulu University Hospital during years 2000-2020. For comparison, samples of 42 non-ampullary adenomas were collected. CAII expression was low in duodenal adenomas and adenocarcinoma. CAIX expression in adenomas and adenocarcinoma was comparable with the high expression of normal duodenal crypts. Expression patterns in carcinomas were largely not related to clinicopathological features. However, low expression of CAII associated with poorer differentiation of the tumor ( p =0.049) and low expression of CAIX showed a trend for association with nodal spread, although statistical significance was not reached ( p =0.091). CAII and CAIX lost their epithelial polarization and staining intensity in adenomas. CAXII expression was not detected in the studied samples. CAs were not associated with survival. The prognostic value of CAII and CAIX downregulation should be further investigated. Both isozymes may serve as biomarkers of epithelial dysplasia in the duodenum.

The aim of our retrospective study was to investigate the expression and clinical significance of the cancer-associated carbonic anhydrases (CAs) II, IX, and XII in Barrett's esophagus and esophageal adenocarcinoma (EAC). We evaluated 101 archival specimens from patients with EAC as well as seven and 26 samples from patients with high-and low-grade dysplasia, respectively. In addition, normal esophageal squamous epithelium, gastric, and intestinal metaplasia were analyzed when present. The expression patterns of isozymes were detected by immunohistochemistry. CAII and CIX expression levels were lower in the squamous epithelium than in the columnar cells while CAXII showed an opposite pattern and was present mainly in squamous epithelium. Expression patterns in benign, dysplastic, or malignant esophageal columnar lesions were not significantly different. The assessment of clinicopathological associations showed that CAII was significantly downregulated in metastatic disease (p = 0.026). CAIX showed no association with prognosis, although there appeared to be an association (p = 0.056) between high expression and nodal spread. In conclusion, CAII, CAIX, and CAXII do not serve as biomarkers for different phases in the development of EAC.