Louis Libbrecht

Bio: Louis Libbrecht is an academic researcher from Université catholique de Louvain. The author has contributed to research in topics: Cancer & Knockout mouse. The author has an hindex of 2, co-authored 8 publications receiving 84 citations. Previous affiliations of Louis Libbrecht include AZ Groeninge & Cliniques Universitaires Saint-Luc.

Endoscopic submucosal dissection specimens in early colorectal cancer: lateral margins, macroscopic techniques, and possible pitfalls

Abstract: Endoscopic submucosal dissection (ESD) allows en-bloc resection of superficial gastrointestinal tumors, providing specimens on which lateral margin analysis can be performed reliably. Positive lateral margins have been linked to higher rates of recurrence/residual tumor. There are no guidelines for macroscopic processing of lateral margins. Currently, most institutions use parallel lateral sections, which are difficult to interpret. We use perpendicular lateral sections, hypothesizing that it decreases potential artifactually positive lateral margins. We analyzed positive lateral margin rates in colorectal ESD specimens according to sectioning method. We also looked at morphological factors associated with margin positivity as a function of technique used. We studied 166 ESD specimens, on which parallel sectioning practiced from 2006 to 2011 (n = 75). Perpendicular sectioning was used from 2010 to 2015 (n = 91). We recorded the number of positive margins, along with grade of dysplasia/carcinoma. Other information such as histopathological type, specimen size, lesion location, and patient follow-up was also recorded for evaluation. Forty of seventy-five (63%) margins were positive for parallel sections. In contrast, perpendicularly cut margins were significantly less frequently positive: 22/91 (24%) (p = 0.0001). Positive margins were found significantly more frequently in tubulo-villous lesions compared to tubular lesions in both the parallel and perpendicular groups (p = 0.03 and p = 0.02, respectively). Specimen size was not significantly associated with positive margins. Using perpendicular sectioning of colorectal ESD specimens, the proportion of cases with a positive lateral margin was significantly lower than when parallel sectioning was used. We suggest perpendicular sectioning to improve accuracy in histopathological analysis. This method is particularly important to use in future studies, as it may prevent authors from making conjectures based on overestimation of positive lateral margins.

Endoscopic features, pathological correlates and possible origin of foveolar gastric metaplasia presenting as a duodenal polyp.

Abstract: It has recently been shown that duodenal foveolar gastric metaplasia (FGM) sometimes presents as a polyp. The mechanism by which FGM develops into a polypoid lesion is unknown and it is unclear whether this form of FGM is indistinguishable from other polypoid lesions or whether endoscopists do not recognize it because they are unfamiliar with it. We identified and retrieved archival cases of FGM endoscopically suspicious for adenomatous polyp and examined their pathological, clinical and endoscopic features. Endoscopic features of the 13 identified FGMs presenting as polyps were heterogeneous and overlapping with those of adenomatous polyps. FGM was frequently associated with mucosal and submucosal Brunner's glands, but defining and recognizing hyperplasia of these glands remains difficult. Other pathological features could not explain the development of a polypoid lesion. The endoscopic features of FGM polyps are non-specific, overlapping with those of adenomatous polyps. FGM polyps probably acquire their polypoid aspect due to association with Brunner's gland hyperplasia (BGH), which also arises due to chronic inflammation and damage. Because BGH is ill-defined and difficult to recognize, while FGM is diagnosed easily, this type of polypoid lesions has until now only been recognized based on the presence of FGM, although FGM is most likely a secondary phenomenon and not the primary cause of the polyp.

Differential Proteomic Analysis of Hepatocellular Carcinomas from Ppp2r5d Knockout Mice and Normal (Knockout) Livers.

Abstract: Background Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Mice lacking the tumor-suppressive protein phosphatase 2A subunit B56δ (Ppp2r5d) spontaneously develop HCC, correlating with increased c-MYC oncogenicity. Materials and methods We used two-dimensional difference gel electrophoresis-coupled matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to identify differential proteomes of livers from wild-type, non-cancerous and HCC-affected B56δ knockout mice. Results A total of 23 proteins were differentially expressed/regulated in liver between wild-type and non-cancerous knockout mice, and 119 between non-cancerous and HCC knockout mice ('cancer proteins'). Overlap with our reported differential transcriptome data was poor. Overall, 56% of cancer proteins were reported before in HCC proteomics studies; 44% were novel. Gene Ontology analysis revealed cancer proteins mainly associated with liver metabolism (18%) and mitochondria (15%). Ingenuity Pathway Analysis identified 'cancer' and 'gastrointestinal disease' as top hits. Conclusion We identified several proteins for further exploration as novel potential HCC biomarkers, and independently underscored the relevance of Ppp2r5d knockout mice as a valuable hepatocarcinogenesis model.

The cell-cell adhesion molecule E-cadherin

Abstract: This review is dedicated to E-cadherin, a calcium-dependent cell-cell adhesion molecule with pivotal roles in epithelial cell behavior, tissue formation, and suppression of cancer. As founder member of the cadherin superfamily, it has been extensively investigated. We summarize the structure and regulation of the E-cadherin gene and transcript. Models for E-cadherin-catenin complexes and cell junctions are presented. The structure of the E-cadherin protein is discussed in view of the diverse functions of this remarkable protein. Homophilic and heterophilic adhesion are compared, including the role of E-cadherin as a receptor for pathogens. The complex post-translational processing of E-cadherin is reviewed, as well as the many signaling activities. The role of E-cadherin in embryonic development and morphogenesis is discussed for several animal models. Finally, we review the multiple mechanisms that disrupt E-cadherin function in cancer: inactivating somatic and germline mutations, epigenetic silencing by DNA methylation and epithelial to mesenchymal transition-inducing transcription factors, and dysregulated protein processing.

Genetic and cell biological analysis of integrin outside-in signaling.

Abstract: Integrins are cell surface transmembrane receptors that recognize and bind to extracellular matrix proteins and counter receptors. Binding of activated integrins to their ligands induces a vast number of structural and signaling changes within the cell. Large, multimolecular complexes assemble onto the cytoplasmic tails of activated integrins to engage and organize the cytoskeleton, and activate signaling pathways that ultimately lead to changes in gene expression. Additionally, integrin-mediated signaling intersects with growth factor-mediated signaling through various levels of cross-talk. This review discusses recent work that has tremendously broadened our understanding of the complexity of integrin-mediated signaling.