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Introduction: Understanding the mutational landscape of colon cancer (CC) is crucial for targeted therapy development. Microsatellite instability (MSI-H), rat sarcoma (RAS), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations (MT) are pivotal markers. Further investigation into clinicopathological features of RAS and BRAF MT in microsatellite stable (MSS) and MSI-H tumors is warranted., Methods: A retrospective analysis of 4883 localized CC patients (pts.) was conducted. Molecular profiling assessed MSI, KRAS, NRAS, and BRAF MT. Correlation with clinicopathological data employed ANOVA and Chi-square tests. Disease-free survival (DFS) and overall survival (OS) were analyzed adjusting for age, gender, sidedness, UICC stage, Charlson Comorbidity Index (CCI). A Cox model incorporated all variables as covariates., Results: This analysis included 4883 pts. (2302 female/2572 male, 3865 (79.2%) MSS, 1018 (20.8%) MSI-H). MSS pts. had more All-Wild Type (WT), KRAS MT, and NRAS MT tumors vs. MSI-H pts. (42.1% vs. 21.1%; 39.8% vs. 15.4%; 3.6% vs. 0.7%; p<0.001 for each). BRAF MT tumors (95.5% BRAF V600E MT) were more prevalent in MSI-H individuals (62.8% vs. 8.1%, p<0.001). KRAS and BRAF MT tumors were more frequently right-sided, while BRAF MT tumors were associated with female gender, advanced disease stage, lymph node positivity, and poorer differentiation in the MSS subset (p<0.001). Common KRAS mutations included p.G12D (30.44%) and p.G12V (21.3%) in MSS and p.G13D (28.9%) and p.G12D (22.37%) in MSI-H. NRAS MT tumors were dominated by codon 61 mutations (51.7%). Survival analysis revealed worst prognosis in BRAF MT MSS tumors (DFS: HR 1.74 (95% CI 1.15-2.62, p=0.009; OS: HR 1.61 (95% CI 0.99-2.6), p=0.055). The 3-years DFS and 5-years OS rates were lowest in this subset (61.6% and 57.7% respectively)., Discussion: These findings highlight the complex interplay between molecular subtypes, clinicopathological features, and survival outcomes in early CC. Further research is needed to elucidate underlying mechanisms and develop personalized treatment strategies., Competing Interests: JC: Advisory Boards: AstraZeneca GmbH, Sanofi-Aventis Deutschland GmbH, Honoraria and Travel Support: AstraZeneca GmbH, Qiagen GmbH, Janssen-Cilag GmbH, MSD Sharp & Dohme GmbH, Merck Healthcare Germany, BS: Trial support institution/study grant institution: BioNTech, SH: Advisory Boards: Fa. Mediglobe ( EUS-KI Project), LM: Travel support: Octapharm, Pierre Fabre, ARS: Honoria: Amgen, Roche, Merck Serono, Bristol-Myers Squibb, MSD, MCI Group, AstraZeneca, Advisory board member: Amgen, AstraZeneca; Bristol-Myers Squibb, Daiichi-Sankyo, Janssen-Cilag, Merck Serono, MSD, Travel support: Roche, Amgen, Pierre Fabre Studies (trial support institution/study grant institution): Roche, Ipsen, Funding for scientific research: Roche, Celgene, Ipsen, Amgen, Alexion Pharmaceuticals, Astra Zeneca, Lilly, Servier, AIO Studien gGmbH, Rafael Pharmaceutics, Erytech Pharma, BioNTech, AT: Trial support institution/study grant institution: BioNTech. The remaining author(s) declare(s) that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ekmekciu, Zucha, Christmann, Wisser, Heuer, Sargin, Hollerbach, Lamberti, Müller, Lugnier, Verdoodt, Denz, Terzer, Feder, Reinacher-Schick, Tannapfel and Tischoff.)

Benign mesothelial tumors are rarer than malignant mesotheliomas and are often found in the peritoneum as incidental findings in women. They include the adenomatoid tumor (AT), the well-differentiated mesothelial tumor (WDPMT), the mesothelioma in situ (MIS), and the solid papillary mesothelial tumor (SPMT). ATs are always benign and predominantly manifest in the genital tract. WDPMTs can develop multifocally and are prone to recurrence, particularly in the case of incomplete resection. Only MISs are considered a confirmed precursor lesion of malignant mesothelioma according to the currently valid World Health Organization (WHO) classifications. As with malignant mesothelioma, alterations of BAP1, MTAP, and p16 are detectable for MIS in contrast to the other three tumors. SPMTs cannot be clearly assigned to the other mesothelial tumors and have so far only been described in the peritoneum in women with a benign course., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

While infrared microscopy provides molecular information at spatial resolution in a label-free manner, exploiting both spatial and molecular information for classifying the disease status of tissue samples constitutes a major challenge. One strategy to mitigate this problem is to embed high-dimensional pixel spectra in lower dimensions, aiming to preserve molecular information in a more compact manner, which reduces the amount of data and promises to make subsequent disease classification more accessible for machine learning procedures. In this study, we compare several dimensionality reduction approaches and their effect on identifying cancer in the context of a colon carcinoma study. We observe surprisingly small differences between convolutional neural networks trained on dimensionality reduced spectra compared to utilizing full spectra, indicating a clear tendency of the convolutional networks to focus on spatial rather than spectral information for classifying disease status.