Boyaval Fanny, Fariña-Sarasqueta Arantza, Boonstra Jurjen J, Heijs Bram, Morreau Hans
Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
Center for Proteomics & Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
Front Med (Lausanne). 2024 Jan 15;10:1221553. doi: 10.3389/fmed.2023.1221553. eCollection 2023.
Pseudoinvasion (PI) is a benign lesion in which cancer is mimicked in the colon by misplacement of dysplastic glands in the submucosa. Although there are morphological clues, the discrimination of PI from true invasion can be a challenge during pathological evaluation of colon adenomas. Both overdiagnosis and underdiagnosis can result in inadequate clinical decisions. This calls for novel tools to aid in cases where conventional methods do not suffice. We performed mass spectrometry imaging (MSI)-based spatial glycomics analysis on a cohort of formalin-fixed paraffin-embedded tissue (FFPE) material from 16 patients who underwent polypectomy. We used this spatial glycomic data to reconstruct the molecular histology of the tissue section using spatial segmentation based on uniform manifold approximation and projection for dimension reduction (UMAP). We first showed that the spatial glycomic phenotypes of the different morphological entities separated as distinct clusters in colon tissues, we separated true invasion from the other morphological entities. Then, we found that the glycomic phenotype in areas with suspected PI in the submucosa was strongly correlating with the corresponding glycomic phenotype of the adenomatous colon epithelium from the same tissue section (Pearson correlation distance average = 0.18). These findings suggest that using spatial glycomics, we can distinguish PI as having a molecular phenotype similar to the corresponding surface epithelium and true invasion as having a different phenotype even when compared to high-grade dysplasia. Therefore, when a novel molecular phenotype is found in the deepest submucosal region, this may be used as an argument in favor of true invasion.
假浸润（PI）是一种良性病变，其中黏膜下层发育异常的腺体错位在结肠中模拟癌症。尽管存在形态学线索，但在结肠腺瘤的病理评估中，将PI与真正的浸润区分开来可能具有挑战性。过度诊断和诊断不足都可能导致临床决策不充分。这就需要新的工具来辅助传统方法不足的情况。我们对16例接受息肉切除术患者的福尔马林固定石蜡包埋组织（FFPE）材料队列进行了基于质谱成像（MSI）的空间糖组学分析。我们使用这些空间糖组学数据，通过基于均匀流形近似和投影进行降维（UMAP）的空间分割来重建组织切片的分子组织学。我们首先表明，结肠组织中不同形态实体的空间糖组学表型分离为不同的簇，我们将真正的浸润与其他形态实体区分开来。然后，我们发现黏膜下层疑似PI区域的糖组学表型与同一组织切片中腺瘤性结肠上皮的相应糖组学表型密切相关（Pearson相关距离平均值 = 0.18）。这些发现表明，使用空间糖组学，我们可以将PI区分开来，其分子表型类似于相应的表面上皮，而真正的浸润即使与高级别发育异常相比也具有不同的表型。因此，当在最深的黏膜下层区域发现一种新的分子表型时，这可以作为支持真正浸润的一个依据。
