{"entity": "researcher", "timestamp": "2026-08-22T07:48:14.227Z", "family": "Lugli", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-9264-5185", "affiliations": ["Institute of Pathology, University of Bern, Bern, Switzerland."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/72f5a2f44c39414db42ebb027c0ffde6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/72f5a2f44c39414db42ebb027c0ffde6"}}, "publications": [{"entity": "publication", "iuid": "26a03d31b8404447b92b85a5f61701b3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/26a03d31b8404447b92b85a5f61701b3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/26a03d31b8404447b92b85a5f61701b3"}}, "title": "Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer.", "authors": [{"family": "Nguyen", "given": "Huu-Giao", "initials": "HG"}, {"family": "Lundstr\u00f6m", "given": "Oxana", "initials": "O"}, {"family": "Blank", "given": "Annika", "initials": "A"}, {"family": "Dawson", "given": "Heather", "initials": "H"}, {"family": "Lugli", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-9264-5185", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/72f5a2f44c39414db42ebb027c0ffde6.json"}}, {"family": "Anisimova", "given": "Maria", "initials": "M"}, {"family": "Zlobec", "given": "Inti", "initials": "I"}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Mod. Pathol.", "issn": "1530-0285", "volume": "35", "issue": "2", "pages": "240-248", "issn-l": "0893-3952"}, "abstract": "The backbone of all colorectal cancer classifications including the consensus molecular subtypes (CMS) highlights microsatellite instability (MSI) as a key molecular pathway. Although mucinous histology (generally defined as >50% extracellular mucin-to-tumor area) is a \"typical\" feature of MSI, it is not limited to this subgroup. Here, we investigate the association of CMS classification and mucin-to-tumor area quantified using a deep learning algorithm, and the expression of specific mucins in predicting CMS groups and clinical outcome. A weakly supervised segmentation method was developed to quantify extracellular mucin-to-tumor area in H&E images. Performance was compared to two pathologists' scores, then applied to two cohorts: (1) TCGA (n = 871 slides/412 patients) used for mucin-CMS group correlation and (2) Bern (n = 775 slides/517 patients) for histopathological correlations and next-generation Tissue Microarray construction. TCGA and CPTAC (n = 85 patients) were used to further validate mucin detection and CMS classification by gene and protein expression analysis for MUC2, MUC4, MUC5AC and MUC5B. An excellent inter-observer agreement between pathologists' scores and the algorithm was obtained (ICC = 0.92). In TCGA, mucinous tumors were predominantly CMS1 (25.7%), CMS3 (24.6%) and CMS4 (16.2%). Average mucin in CMS2 was 1.8%, indicating negligible amounts. RNA and protein expression of MUC2, MUC4, MUC5AC and MUC5B were low-to-absent in CMS2. MUC5AC protein expression correlated with aggressive tumor features (e.g., distant metastases (p = 0.0334), BRAF mutation (p < 0.0001), mismatch repair-deficiency (p < 0.0001), and unfavorable 5-year overall survival (44% versus 65% for positive/negative staining). MUC2 expression showed the opposite trend, correlating with less lymphatic (p = 0.0096) and venous vessel invasion (p = 0.0023), no impact on survival.The absence of mucin-expressing tumors in CMS2 provides an important phenotype-genotype correlation. Together with MSI, mucinous histology may help predict CMS classification using only histopathology and should be considered in future image classifiers of molecular subtypes.", "doi": "10.1038/s41379-021-00894-8", "pmid": "34475526", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8786661"}, {"db": "pii", "key": "S0893-3952(22)00335-0"}], "notes": [], "created": "2026-08-21T11:46:58.086Z", "modified": "2026-08-21T11:46:58.157Z"}]}