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Introduction: MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and contribute to the development of cancer. They have been shown to be stable in tissue samples and may be promising diagnostic biomarkers for endometrial cancer., Material and Methods: A retrospective cohort study of women diagnosed with endometrial cancer between January 2017 and December 2017 was performed at the Royal Cornwall Hospital. Archived formalin-fixed paraffin-embedded samples were obtained from patients with endometrial cancer and healthy women. MicroRNA was isolated and quantitative real-time polymerase chain reaction was used to detect expression levels of miRNAs., Results: A total of 76 women were included: 36 endometrial cancer patients, 40 healthy controls. A distinct panel of miR-200a, miR-200b, miR-200c, miR-205, and miR-182 showed an area under the curve of 0.958, sensitivity 92%, specificity 89%, positive predictive value of 89% (95% CI 82%-94%) and negative predictive value of 91% (95% CI 85%-96%) in diagnosing endometrial cancer. High miR-182 expression levels were significantly related to high-grade endometrioid tumors compared with low-grade tumors., Conclusions: We demonstrated high diagnostic accuracy of miRNA for detecting endometrial cancer. In addition, miRNA contributed to an improvement in distinguishing between high-grade and low-grade endometrioid tumors., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Richter transformation (RT) is defined as development of aggressive lymphoma in patients (pts) with CLL. The incidence rates of RT among pts with CLL range from 2 to 10%. The aim of this analysis is to report the frequency, characteristics and outcomes of pts with RT enrolled in trials of the GCLLSG. A total of 2975 pts with advanced CLL were reviewed for incidence of RT. Clinical, laboratory, and genetic data were pooled. Time-to-event data, starting from time of CLL diagnosis, of first-line therapy or of RT diagnosis, were analyzed by Kaplan-Meier methodology. One hundred and three pts developed RT (3%): 95 pts diffuse large B-cell lymphoma (92%) and eight pts Hodgkin lymphoma (8%). Median observation time was 53 months (interquartile range 38.1-69.5). Median OS from initial CLL diagnosis for pts without RT was 167 months vs 71 months for pts with RT (HR 2.64, CI 2.09-3.33). Median OS after diagnosis of RT was 9 months. Forty-seven pts (46%) received CHOP-like regimens for RT treatment. Three pts subsequently underwent allogeneic and two pts autologous stem cell transplantation. Our findings show that within a large cohort of GCLLSG trial participants, 3% of the pts developed RT after receiving first-line chemo- or chemoimmunotherapy. This dataset confirms the ongoing poor prognosis and high mortality associated with RT.

Disease progression in myelodysplastic syndromes (MDS) and myelodysplastic-myeloproliferative neoplasms (MDS/MPN) is a major source of mortality. The European Bone Marrow Working Group organized a dedicated workshop to address MDS and MDS/MPN progression, and myeloid neoplasms with histiocytic and lymphoblastic outgrowths in 2019 in Frankfurt, Germany. In this report, we summarize clinical, histopathological, and molecular features of 28 cases. Most cases illustrate that prognostic mutational profiles change during follow-up due to accumulation of high-risk mutations in the trunk clone, and that results from repeated molecular testing can often explain the clinical progression, suggesting that regular genetic testing may predict transformation by early detection of aggressive clones. Importantly, identical mutations can be linked to different clinical behaviors or risks of fibrotic progression and/or transformation in a context-dependent manner, i.e., MDS or MDS/MPN. Moreover, the order of mutational acquisition and the involved cell lineages matter. Several cases exemplify that histiocytic outgrowths in myeloid neoplasms are usually accompanied by a more aggressive clinical course and may be considered harbinger of disease progression. Exceptionally, lymphoblastic transformations can be seen. As best estimable, the histiocytic and lymphoblastic compounds in all occasions were clonally related to the myeloid compound and-where studied-displayed genomic alterations of, e.g., transcription factor genes or genes involved in MAPK signaling that might be mechanistically linked to the respective type of non-myeloid outgrowth.

Within the last decade, there has been a tremendous progress in understanding the molecular basis of cancer. In particular, the development and the characteristic features of cancer cells are being increasingly understood. The understanding of these molecular characteristics is mandatory for the development of novel, targeted therapeutic strategies and their integration into clinical practice. In addition, tumour genetics play a critically important role for hereditary cancer syndromes, with respect to both diagnostics and clinical decision-making. The aim of this review is to highlight general principles of tumour genetics from a visceral surgeon's point of view, although a comprehensive summary of all aspects would be beyond the scope of this article due to the complexity of the topic., (Georg Thieme Verlag KG Stuttgart · New York.)

The Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC; www.helmholtz-pccc.de) hosted the "1st International Kloster Seeon Meeting on Mouse Models of Human Cancer" in the Seeon monastery (Germany) from March 8 to 11, 2014. The meeting focused on the development and application of novel mouse models in tumor research and high-throughput technologies to overcome one of the most critical bottlenecks in translational bench-to-bedside tumor biology research. Moreover, the participants discussed basic molecular mechanisms underlying tumor initiation, progression, metastasis, and therapy resistance, which are the prerequisite for the development of novel treatment strategies and clinical applications in cancer therapy., (©2014 American Association for Cancer Research.)

According to many authors, the treatise on cancer written by Theodor Boveri in 1914 demonstrates astonishing foresight with respect to contemporary cancer research, in particular with respect to the genomic instability of tumors. In some recent publications, however, it has been claimed that not Boveri but primarily David von Hansemann deserves credit for these chromosomal theories of cancer origin. The claim seems to be unjustified because there are great differences, both in conception and in argumentation, between both opinions. In addition, it has been ignored that von Hansemann himself said that his views "were corrected and developed further by Boveri". In this paper two obviously unknown comments regarding Boveri's theory by von Hansemann are presented as examples. Furthermore, the paper points out that the pathologist von Hansemann was engaged in the formal genesis of tumors using descriptive methods. By contrast, the embryologist Boveri developed his hypotheses on the basis of the experimentally founded chromosome theory of inheritance in an attempt to explain the etiology or causal genesis of tumors. Thus, it can be concluded that Boveri developed the first genetic cancer theory in the history of medicine.

The Jena Institute of Pathology has been serving as a consultation and reference center for soft tissue tumors in Germany since 1978. The present study provides an overview of the clinicopathological data from a two-year period and an update on diagnostics and research. Retrospectively, 7043 cases sent to the institute in the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate, 35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms with fibroblastic differentiation were the most frequent. The mean age of patients with a sarcoma was 63 years. The molecular pathological analysis of soft tissue tumors has attained a major role in diagnosis. This is further advanced at the Jena institute in the context of a German Federal Ministry of Education and Research (BMBF) project for molecular sarcoma diagnosis with the aim of developing and validating DNA probes for in situ hybridization detection of translocations and their associated chromosomal breaks on the one hand, and DNA chips for the detection of fusion transcripts on the other. Research projects relate to the analysis of specific biomarkers in large tumor collectives and the pathomechanisms in several sarcoma entities.

Background: Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up to investigate the role of candidate genes in the susceptibility to lung cancer patients younger than 51 years at diagnosis., Methods: 246 patients with a primary, histologically or cytologically confirmed neoplasm, recruited from 2000 to 2003 in major lung clinics across Germany, were matched to 223 unrelated healthy controls. 11 single nucleotide polymorphisms of genes with reported associations to lung cancer have been genotyped., Results: Genetic associations or gene-smoking interactions was found for GPX1(Pro200Leu) and EPHX1(His113Tyr). Carriers of the Leu-allele of GPX1(Pro200Leu) showed a significant risk reduction of OR = 0.6 (95% CI: 0.4-0.8, p = 0.002) in general and of OR = 0.3 (95% CI:0.1-0.8, p = 0.012) within heavy smokers. We could also find a risk decreasing genetic effect for His-carriers of EPHX1(His113Tyr) for moderate smokers (OR = 0.2, 95% CI:0.1-0.7, p = 0.012). Considered both variants together, a monotone decrease of the OR was found for smokers (OR of 0.20; 95% CI: 0.07-0.60) for each protective allele., Conclusion: Smoking is the most important risk factor for young lung cancer patients. However, this study provides some support for the T-Allel of GPX1(Pro200Leu) and the C-Allele of EPHX1(His113Tyr) to play a protective role in early onset lung cancer susceptibility.

Our aim was to determine the spectrum and accumulation of mutations in surveillance biopsies from Barrett's mucosa of individual patients during follow-up. We performed loss of heterozygosity (LOH) analysis of six recently described tumor suppressor genes relevant for the carcinogenesis of Barrett's adenocarcinoma from laser-microdissected, paraffin-embedded biopsy samples of Barrett's mucosa without or with low-grade dysplastic change. 118 biopsy samples from 26 patients were taken during surveillance programs in time intervals ranging between 6 and 51 months. We found no significant increase in LOH events at least in a 51-month interval. In two patients, Barrett's adenocarcinoma was diagnosed 6 months after the first diagnosis of Barrett's mucosa. Six of 26 patients did not show LOH. The remaining patients exhibited a striking variation of LOH patterns and accumulations in biopsy samples during follow-up. From our microsatellite marker panel, we were not able to define a single surrogate marker that could serve as a potential biomarker, indicating an increased risk of progression to Barrett's adenocarcinoma. However, LOH combinations, especially APC/p16(INK4) or APC/p53, deserve attention as putative biomarkers in future studies. Our results raise important questions regarding the biological dynamics of mutations in Barrett's mucosa in addition to the influence of sampling, especially with regard to the number of biopsies taken from Barrett's mucosa.

Soft tissue malignancies in childhood and adolescence encompass a wide variety of histologically and genetically different tumor entities. In the files of the Kiel Pediatric Tumor Registry, 4,272 soft tissue malignancies were collected since 1977. Rhabdomyosarcomas are by far the most frequent sarcomas (44.6 % of the cases), followed in decreasing order of frequency by the family of Ewing tumors (peripheral primitive neuroectodermal tumors and extraosseous Ewing's sarcomas; altogether 22.3 %), malignant peripheral nerve sheath tumors (8.1 %), synovial sarcomas (5.0 %), leiomyosarcomas (3.2 %), fibrosarcomas (2.4 %), extrarenal malignant rhabdoid tumors (2.0 %), and alveolar soft tissue sarcomas (1.1 %). A further group (11.3 %) includes rare tumors, intermediate fibrohistiocytic tumors, and unclassified sarcomas. Embryonal rhabdomyosarcomas are 2.5 times more frequent than the alveolar rhabdomyosarcomas, which are prognostically unfavorable and located predominantly in the extremities and the trunk. With regard to clinical findings, histology, molecular biology and prognosis, embryonal and alveolar rhabdomyosarcomas have to be considered as two different tumor types. The family of Ewing tumors includes extraosseous Ewing's sarcoma and peripheral primitive neuroectodermal tumors (synonym: malignant peripheral neuroectodermal tumors), the former tumors without and the latter with neural differentiation. Many cases of infantile malignant peripheral nerve sheath tumors and infantile fibrosarcomas are low-grade malignancies and prognostically more favorable than their "adult" counterparts.

Geographical differences have been demonstrated for the cancer incidence and histology of differentiated thyroid cancer. Iodine intake and specific external noxes, such as nitrosamine ingestion or external radiation are important factors. It is still questionable whether histologically identical differentiated thyroid cancers are prognostically different in low and rich iodine areas. Despite increased knowledge of molecular and genetic changes in differentiated cancer, the present therapy is primarily related to patient age, tumor stage and histology.