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.
摘要：
在结直肠肿瘤中异位骨化（HO）的生物学机制和潜在的临床影响尚不完全清楚。这项研究调查了与HO相关的结直肠肿瘤的临床病理特征，并研究了骨形态发生蛋白（BMP）途径在HO发展中的潜在作用。对表现出HO及其与共有分子亚型(CMS)的关联的结肠直肠癌(CRC)进行基于人工智能(AI)的分类。该研究通过荷兰全国病理学数据库纳入了77例病例。对BMP2、SMAD4和Osterix进行免疫组织化学。AI算法评估肿瘤-基质比率以近似CMS。文献检索产生了96例病例报告，对其进行了分析，并与我们的病例进行了临床病理参数比较。HO在我们的队列中更常见地观察到传统的锯齿状腺瘤（25％），肾小管绒毛状腺瘤（25%）和幼年性息肉（25%），而在文献中，它最常见于幼年性息肉（38.2％）和炎性息肉（29.4％）。在这两个队列中，大多数是常规癌(>60%),其次是粘液性和锯齿状腺癌.在直接围绕骨的肿瘤和/或基质细胞中观察到BMP2，SMAD4和Osterix的较高表达，表明BMP途径的激活。肿瘤基质分析指定>50%的病例为间充质亚型(CMS4)(59%)。HO对锯齿状和幼年/炎性息肉有好感，粘液和锯齿状腺癌。BMP信号被激活，似乎在结直肠肿瘤中HO的形成中起作用。符合与CMS4CRC相关的TGFβ/BMP途径激活，HO似乎与CMS4有关。
