65th Annual Meeting of the German Society of Neuropathology and Neuroanatomy (DGNN) - Meeting Abstracts, September 1–3, 2021

Dear participants, dear colleagues, It is our great pleasure to welcome you to the 65th Annual Meeting of the German Society of Neuropathology and Neuroanatomy - the brain and nerve microenvironment in health and disease - which will be held as a virtual meeting from September 1–3, 2021. The meeting will bring together basic and clinical researchers, physicians as well as junior scientists and PhD students from different disciplines of basic and clinical neuroscience. We will have outstanding lectures by and with some of the most renowned international experts in the field of neuro-oncology, neuroinflammation, neurodegeneration and muscle and nerve diseases and look forward to exciting scientific discussions. There will also be a special and timely section on the effects of COVID-19 on the central and peripheral nervous system. The three days will offer exciting insights into different areas of basic and clinical neuroscience. We have also encouraged early career scientists to present their scientific findings in short talks and poster presentations. We are therefore particularly thankful that the abstracts of the meeting, which in their sum provide the best overview of the high scientific standing of the field, will be published in Free Neuropathology. Finally, we would like to thank you all for your active contribution to this conference in these difficult times. We also thank all supporters for their financial help. We wish you a stimulating and exciting conference. Yours sincerely, Prof. Dr. med. Till Acker Conference Chair (Justus Liebig University Giessen Dr. med. Anne Schänzer Dr. med. Hildegard Dohme

Radio-Pathomic Approaches in Pediatric Neurooncology: Opportunities and Challenges

With medical software platforms moving to cloud environments with scalable storage and computing, the translation of predictive artificial intelligence (AI) models to aid in clinical decision-making and facilitate personalized medicine for cancer patients is becoming a reality. Medical imaging, namely radiologic and histologic images, has immense analytical potential in neuro-oncology, and models utilizing integrated radiomic and pathomic data may yield a synergistic effect and provide a new modality for precision medicine. At the same time, the ability to harness multi-modal data is met with challenges in aggregating data across medical departments and institutions, as well as significant complexity in modeling the phenotypic and genotypic heterogeneity of pediatric brain tumors. In this paper, we review recent pathomic and integrated pathomic, radiomic, and genomic studies with clinical applications. We discuss current challenges limiting translational research on pediatric brain tumors and outline technical and analytical solutions. Overall, we propose that to empower the potential residing in radio-pathomics, systemic changes in cross-discipline data management and end-to-end software platforms to handle multi-modal data sets are needed, in addition to embracing modern AI-powered approaches. These changes can improve the performance of predictive models, and ultimately the ability to advance brain cancer treatments and patient outcomes through the development of such models

A study of the molecular pathology of ductal carcinoma in situ and invasive ductal carcinoma of the breast.

The biological validity of the histopathological classification of ductal carcinoma in situ (DCIS) of the breast was evaluated in this study by correlating the three histopathological grades of DCIS to immunohistochemical expression of Ki67, p53, cerbB-2, markers of poor prognosis in invasive ductal carcinoma (IDC) and also to bcl2 and ER, markers of good prognosis in invasive breast cancer. DCIS grades correlated positively to Ki67, p53, cerbB-2 and negatively to bcl2 and ER, suggesting validity of the classification. The incidence of bax protein expression was determined immunohistochemically in DCIS and IDC. It did not correlate to histopathological grades of DCIS or IDC. The relationships of bax protein to the above mentioned biological markers were also determined in DCIS and IDC. Furthermore, the expression of bax, bcl2, Ki67, ER, p53 and cerbB-2 within DCIS grades was compared with the expression of these markers within IDC grades. The DCIS grades were determined subjectively as well as objectively by means of computer assisted image analysis with significant correlation found between subjective and objective measures. Image analysis was also used to determine percentage of positive cells per case for the nuclear stains (Ki67, ER, p53). Immunohistochemically positive p53 cases were analysed for p53 mutation by polymerase chain reaction (PCR) and subsequent DNA sequencing to compare the incidence of p53 mutation in DCIS to that of IDC. Biochemical changes within tissue may either initiate disease or occur as the result of the disease process and these changes can be studied by both Fourier transform infrared (FTIR) and FT-Raman spectroscopic techniques. FTIR and FT-Raman were employed to distinguish the DCIS and IDC grades. It has the potential to distinguish between DCIS grades, between IDC grades and also between DCIS and IDC as whole groups. The implications of the obtained data for the understanding of the molecular biology of DCIS of the breast and IDC are discussed and future investigations to further elucidate the molecular and cellular mechanisms involved are proposed

Targeting Wnt Signaling in Cancer: Opportunities Abound If We Can Avoid the Sword of Damocles

Dysregulation of Wnt signaling is known to be associated with various cancers. As such, identification of novel Wnt pathway targets in cancer and better characterization of already-known targets present exciting, emerging opportunities for cancer treatment. In this Special Issue, we feature papers which discuss the role of Wnt signaling and associated targets in cancer metabolism, tumor immune response, and tumor microenvironment. Papers discussing a range of Wnt-mediated cancers, including those of the colon, liver, pancreas, synovium, bladder, etc., are included

Involvement of the WT1 and p16 genes in Wilms' tumour and human malignant mesothelioma

Normal cellular homeostasis is established and maintained by the positive and negative regulatory activities of many genes. When these genes are mutated to forms that can contribute to tumorigenesis, either by dominant, gain of function mutations in positive regulators or recessive, loss of function mutations in negative regulators, they are termed oncogenes or tumour suppressor genes, respectively. Identified human tumour suppressor genes, though still relatively few in number, are found to be active in many different cellular processes. I have studied two such genes, the WT1 and p16 genes, which in their wild type forms are known to contribute to development of the urogenital system and the mesothelium (WTI) and to control of the cell cycle (pi6).WT1 was identified as a gene repeatedly disrupted in Wilms' tumour, a common paediatric renal malignancy. This study is one of many which sought to confirm and understand some of the roles of WTI in both normal development and tumorigenesis. Mutation analysis of WTI in samples from patients with sporadic, bilateral and syndrome-associated Wilms' tumour has produced a pattern of results consistent with the findings of other groups. No mutations were detected in the sporadic and bilateral tumours, however exonic point mutations were detected in 7 out of 9 syndrome-associated Wilms' tumour samples that were analysed in detail. Studies examining parental WTI status, genomic imprinting and allele loss distal to the WTI locus are detailed for the syndrome-associated Wilms' tumour samples. Additionally, analysis of WTI in samples from patients with testicular tumours or malignant mesothelioma did not identify any mutations believed to be significant in tumorigenesis.The contribution, resulting effects and complementary nature of WTI and p16 mutations in Wilms' tumour and malignant mesothelioma is discussed