47 research outputs found
Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability
No full textContext. - Criteria for microsatellite instability (MSI) testing to rule out hereditary nonpolyposis colorectal cancer were recently revised and include parameters such as age and specific histologic features that can be identified by the pathologist, triggering reflex MSI testing. Objective. - To review the performance of the revised Bethesda guidelines to identify MSI-positive colorectal cancers. Design. - Seventy-five patients with colorectal cancer were included; 68 patients younger than 50 years and 7 patients between 50 and 60 years were selected based on histopathologic criteria. Microsatellite instability testing with the National Cancer Institute-recommended panel and immunohistochemistry for hMLH1 and hMSH2 were performed. Tumors were classified into microsatellite instability high (MSI-H), low (MSI-L), or stable (MSS) categories. Results. - Overall, 17 (23%) of 75 colorectal cancer cases were classified as MSI-H, including 13 patients younger than 50 years and 4 patients between 50 and 60 years. Among the MSI-H tumors, 10 (59%) were characterized by loss of hMLH1 and 6 (35%) were hMSH2 negative. Histologic features suggestive of MSI-H phenotype were present in 80% of MSI-H and 35% of MSS/MSI-L tumors. The number of positive lymph nodes was higher in MSS/MSI-L adenocarcinomas (P = .04). Conclusions. - By selecting for age and histologic features, we detected MSI-H tumors in approximately one quarter of colorectal cancer cases meeting the revised Bethesda guidelines and identified 17 MSI-H cases, whereas only 8 would have been recognized by the prior guidelines. These data indicate that reflex testing requested by pathologists based on the revised Bethesda guidelines increases the detection of MSI-H and potential hereditary nonpolyposis colorectal cancer cases
Analysis of genomic instability using multiple assays in a patient with Rothmund-Thomson syndrome
No full textWe report on a patient with Rothmund-Thomson syndrome (RTS) whose cytogenetic evaluation showed a normal karyotype with no evidence of trisomy mosaicism or chromosomal rearrangements. Cultured lymphocytes from the patient, her mother, and a control exposed to mitomycin C and diepoxybutane did not show increased sensitivity to the dialkylating agents. Unlike some previous reports, we found no evidence of a deficiency in nucleotide excision repair, as measured with the functional unscheduled DNA synthesis assay. Glycophorin A analysis of red blood cells for somatic mutation revealed suspiciously high frequencies of both allele loss and loss-and-duplication variants in the blood of the patient, a pattern consistent with observations in other RecQ-related human diseases, and evidence for clonal expansion of a mutant clone in the mother. Discrepant results in the literature may reflect true heterogeneity in the disease or the fact that a consistent set of tests has not been applied to RTS patients
Comparison of Locoregional Recurrence with Mastectomy vs. Breast Conserving Surgery in Pregnancy Associated Breast Cancer (PABC)
No full textAbstract: We have compared outcomes, including the locoregional recurrence, between mastectomy and breast conserving therapy in PABC. Patients were divided into those who were treated with mastectomies (group 1) and those with breast conserving surgery (group 2). The groups were comparable except for lower mean age in group 2 and more patients with stage III disease and higher number of nodes positive in the group 1. Five-year actuarial LRR, distant metastases free survival and overall survival in group 1 vs. 2 were 10 % vs
Genotype-phenotype correlations of pheochromocytoma in two large von Hippel-Lindau (VHL) type 2A kindreds with different missense mutations
No full textLong-term outcomes, branch-specific expressivity, and disease-related mortality in von Hippel-Lindau type 2A
No full textA case-only study to identify genetic modifiers of breast cancer risk for <em>BRCA1/BRCA2</em> mutation carriers
No full text\ua9 2021, The Author(s).Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers
Technical education and the London county council 1918-1939. A study in course innovation and development
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Our thesis is concerned with the process of course innovation and Development in technical education within the area of the London County Council During the period 1918-39. Although essential, an historical study, the Thesis is intended to be of value in a consideration of future development in Technical education, and in particular in the study of the relationship between Curriculum management and manpower planning. The first part of our thesis describes the institutional structure of the principal sectors of technical education in London and outlines the Type of courses that were available and their general progress during the Interwar years. The second part of our thesis seeks to analyse the background to course innovation and to assess why certain courses were successful and why others were comparative failures. Since the topic is potentially so vast, our thesis has been limited to an identification of major factors, rather than a detailed consideration of each one. Our analysis shows the process of course innovation and development in technical education to have been a highly complex interaction of forces in which the other aspects of the educational structure, including administrative as well as teach1ng institutions, played a vital role. Emphasis has been given to the influence of senior administrative officers within the local I education authority framework. Special mention has been made of the work of the Board of Education and of the limitations of the Board in tailing to establish definite guidelines for course development in technical education. Important factors outside the educational structure have also been considered, including the attitudes of parents and business management to formal technical training
Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
No full textA Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4
Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
No full textA Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4
