Carbonic anhydrases II, IX, and XII in esophageal and duodenal diseases

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Oulu University Hospital, Lecture Hall 1. Remote access: https://oulu.zoom.us/j/66127028063

Topic of the dissertation

Carbonic anhydrases II, IX, and XII in esophageal and duodenal diseases

Doctoral candidate

Licenciate of Medicine Minna Nortunen

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Cancer and Translational Medicine Research Unit and Department of Surgery

Subject of study

Medicine

Opponent

Professor Caj Haglund, University of Helsinki

Custos

Professor Juha Saarnio, University of Oulu

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New knowledge on diseases of esophagus and duodenum

The thesis investigated the immunohistochemical expression of carbonic anhydrases (CAs) II, IX and XII, acid-base controlling enzymes of the body, in esophageal and duodenal diseases. The aim was to determine, whether CAs have a role in the pathophysiology of gastrointestinal reflux disease (GERD) or if they can be considered as prognostic biomarkers in esophageal or duodenal cancers.

GERD is a very common condition with an increasing trend in incidence due to obesity pandemic. Chronic GERD may then lead to replacement of the squamous esophageal epithelium by intestinal or gastric columnar epithelium, which is referred to as Barrett's esophagus. Barrett's esophagus is a known precursor of esophageal adenocarcinoma. Esophageal cancer has a poor prognosis still today: according to the Finnish Cancer Registry report form 2019, the relative 5-year survival is only 15% in men, and 20% in women. Despite advances in surgical techniques, only few prognostic biomarkers are available for guiding clinical practice in esophageal cancer.

The study found, that CAs are strongly expressed in reflux esophagitis, in comparison to normal esophagus, and they may participate in the esophageal defense against acidic reflux. In Barrett's esophagus, CA expression was characteristic to each isoenzyme, but they did not seem to serve as markers of precancerous lesions. CAs could not be identified as prognostic biomarkers in esophageal adenocarcinoma, although some clinicopathological features, such as presence of distant metastases, associated with expression levels of isoenzymes II and IX.

Duodenal cancer is a very rare malignancy, and thus only little information is available on its prognostic biomarkers. The thesis studied the expression of CAs in benign duodenal adenomas and in duodenal cancer. It was found that expressions of CAII and CAIX may serve as markers of precancerous areas in duodenal adenomas, but any prognostic effect in duodenal cancer could not be shown. Possibly, with a larger dataset, CAIX could be identified as a biomarker of favorable prognosis.
Last updated: 1.3.2023