Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Mar:145:34-41.
doi: 10.1016/j.humpath.2024.02.006. Epub 2024 Feb 15.

Biological background of colorectal polyps and carcinomas with heterotopic ossification: A national study and literature review

Anne-Marie Vos  1 , Lieke Pijnenborg  2 , Shannon van Vliet  2 , Liudmila L Kodach  3 , Francesco Ciompi  2 , Rachel S van der Post  2 , Femke Simmer  2 , Iris D Nagtegaal  2
Affiliations
Free article
Review

Biological background of colorectal polyps and carcinomas with heterotopic ossification: A national study and literature review

Anne-Marie Vos et al. Hum Pathol. 2024 Mar.
Free article

Abstract

The biological mechanisms and potential clinical impact of heterotopic ossification (HO) in colorectal neoplasms are not fully understood. This study investigates the clinicopathological characteristics of colorectal neoplasms associated with HO and examines the potential role of the bone morphogenetic protein (BMP) pathway in development of HO. An artificial intelligence (AI) based classification of colorectal cancers (CRC) exhibiting HO and their association with consensus molecular subtypes (CMS) is performed. The study included 77 cases via the Dutch nationwide Pathology databank. Immunohistochemistry for BMP2, SMAD4, and Osterix was performed. An AI algorithm assessed the tumour-stroma ratio to approximate the CMS. A literature search yielded 96 case reports, which were analysed and compared with our cases for clinicopathological parameters. HO was more frequently observed in our cohort in traditional serrated adenomas (25%), tubulovillous adenomas (25%) and juvenile polyps (25%), while in the literature it was most often seen in juvenile polyps (38.2%) and inflammatory polyps (29.4%). In both cohorts, carcinomas were mostly conventional (>60%) followed by mucinous and serrated adenocarcinomas. Higher expression of BMP2, SMAD4, and Osterix was observed in tumour and/or stromal cells directly surrounding bone, indicating activation of the BMP pathway. The tumour-stroma analysis appointed >50% of the cases to the mesenchymal subtype (CMS4) (59%). HO has a predilection for serrated and juvenile/inflammatory polyps, mucinous and serrated adenocarcinomas. BMP signalling is activated and seems to play a role in formation of HO in colorectal neoplasms. In line with TGFβ/BMP pathway activation associated with CMS4 CRC, HO seems associated with CMS4.

Keywords: Bone morphogenetic protein; Colorectal cancer; Colorectal polyp; Epithelial mesenchymal transition; Heterotopic ossification.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest No potential conflicts of interest relevant to this article were reported.

Similar articles

See all similar articles

LinkOut - more resources