Carbonic Anhydrases II and IX in Non-ampullary Duodenal Adenomas and Adenocarcinoma

Abstract

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 CO2 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. (J Histochem Cytochem XX: XXX–XXX, XXXX)

Primary Duodenal Adenocarcinoma Expressing Carbonic Anhydrase IX

“…In the other, CA9 was shown to be expressed in 70% of all duodenal adenocarcinomas evaluated, with the level of its expression shown to be comparable to that in normal duodenal crypts. Furthermore, CA9 overexpression tended to be associated with the absence of regional lymph node metastasis [5]. In the present case, the duodenal adenocarcinoma was shown to be well differentiated and localized with no lymph node metastasis, with the level of CA9 expression being comparable to that in the normal duodenal mucosa.…”

“…To date, two studies of CA9-expressing duodenal adenocarcinomas have been reported [5, 7]. In one study, CA9 was shown to be not only expressed in 36% (63/175) of all small intestine cancers evaluated ( n = 175) including duodenal cancers ( n = 95) but significantly more highly expressed in well- and moderately differentiated tumors than in poorly differentiated tumors, tumors with no lymph node metastasis, and low-stage carcinomas.…”

“…Carbonic anhydrase IX (CA9) is a stable transmembrane zinc metalloenzyme and plays an important role in the growth and survival of tumor cells under hypoxia [2, 3]. CA9 has been reported to be expressed in the normal epithelium of the stomach, duodenum, and jejunum [4], as well as in various cancers such as head and neck, gastric, rectum, breast, and ovarian cancers [5]. Therefore, CA9 appears to represent a promising target that interferes with tumor pH regulation and energy metabolism [6], while CA9 expression in duodenal adenocarcinomas remains poorly elucidated.…”

A Case of Duodenal Adenocarcinoma Effectively Highlighted by Linked Color Imaging and Confirmed by Histopathology

“…Also of note in the present case was that CA9 may prove a viable prognostic marker for duodenal adenocarcinoma as a stable transmembrane zinc metalloenzyme shown to play a key role in tumor metabolism [10,11]. In studies of CA9-expressing duodenal adenocarcinomas published to date [12,13], CA9…”

“…expression was reported to be significantly correlated with better tumor differentiation, no lymph node metastasis, tumor downgrading, and no perineural and lymphatic invasion [12], while CA9 overexpression tended to be associated with no regional lymph node metastasis [13].…”