Aneuploidy characterizes adjacent non-malignant mucosa of ulcerative colitis-associated but not sporadic colorectal carcinomas: a matched-pair analysis

Abstract

Introduction. Aneuploidy has been suggested as independent prognostic marker in ulcerative colitis (UC) patients for developing UC-associated colorectal carcinomas (UCCs). UCCs are associated with a poorer prognosis and more frequently present with synchronous carcinomas when compared with sporadic colorectal carcinomas (SCCs). The authors therefore investigated if the adjacent non-malignant mucosa of aneuploid UCCs and aneuploid SCCs shows differences regarding the frequency of aneuploidy and if this aneuploidy is associated with histomorphological alterations. Methods. Primary tumors of 25 UCCs and 20 SCCs were selected showing exclusively aneuploid DNA patterns and matching DNA stemlines. The UCCs' (n = 82) and SCCs' (n = 40) adjacent non-malignant mucosa were evaluated for histopathology and assessed for DNA ploidy status by image cytometry. Results. UCCs' non-malignant mucosa showed dysplasia in 31.7% and aneuploidy in 89%. In contrast, SCCs' non-malignant mucosa revealed no dysplasia and aneuploidy in only 5%. Irrespective of dysplastic lesions, aneuploidy was observed more frequently in adjacent non-malignant mucosa of UCCs than of SCCs (p < 0.001). Neither a correlation between aneuploidy and inflammation (p = 0.916) nor between aneuploidy and dysplastic lesions (p = 0.159) could be observed. Conclusion. Aneuploidy is more frequent in adjacent non-malignant mucosa of aneuploid UCCs than in adjacent non-malignant mucosa of aneuploid SCCs. Furthermore, aneuploidy seems to be irrespective of inflammation or dysplasia. The results therefore emphasize the importance of aneuploidy for UC-associated carcinogenesis and its potential as new diagnostic target.

Key Words::

• adjacent non-malignant mucosa
• colorectal cancer
• dysplasia
• non-malignant mucosa
• ploidy
• ulcerative colitis-associated carcinoma

Acknowledgements

The authors would like to thank Claudia Killaitis for clinical data management, Gisela Grosser-Pape for excellent technical assistance with image cytometry and Elke Gheribi and Regina Kaatz for clinical sample collection. Grants from the Ad Infinitum Foundation, the Werner and Clara Kreitz Foundation and the H.W. & J. Hector Foundation are gratefully acknowledged. KF Meyer received a personal stipend by the Ad Infinitum Foundation. This work was performed in collaboration with the Surgical Center for Translational Oncology-Lübeck (SCTO-L) and the North German Tumor Bank of Colorectal Cancer (ColoNet), the latter one generously funded by the German Cancer Aid Foundation (DKH #108446).

Declaration of interest: None of the data have been communicated previously. All authors declare that they have no competing financial interest.