The prevalence of microsatellite instability in head and neck squamous cell carcinoma

PURPOSE: The present study aimed to use the most definitive available techniques to resolve controversy in the literature as to the prevalence of microsatellite instability (MSI) in head and neck squamous cell carcinoma (HNSCC). METHODS: Eighty patients with advanced HNSCC were enrolled in the study that examined 20 microsatellite markers with automatic fragment analysis. These markers included ones derived from the NCI reference panel and ones previously reported to detect MSI in HNSCC (HNSCC panel). RESULTS: Only one of 80 tumors could be considered positive for MSI. For this case, both panels showed MSI-High (8/10 positive markers for the NCI reference panel and 6/10 positive markers for the HNSCC panel). Qualitatively, the observed MSI could be classified as Type B MSI. CONCLUSIONS: The present results indicate that MSI has a low prevalence in HNSCC.status: publishe

Study of the possible association of HLA class II, CD4, and CD3 polymorphisms with schizophrenia

In the present study the HLA-DRB and DPB1 alleles as well as CD4 and CD3 polymorphisms were tested in 100 Belgian schizophrenic patients and 204 controls. Our results indicate a significant negative association of the DPB1 0101 allele with schizophrenia (relative risk [RR] = 0.27). Furthermore a significant positive and negative association could be noticed for the CD4*A4 allele and CD4*A7/A8 genotype, respectively (RR 1.79 and 0.47, respectively). These findings suggest that some contribution of HLA class II and CD4 genes to an autoimmune-like pathogenesis in schizophrenia might exist.status: publishe

Keratinocytic epidermal nevus syndrome with Schwann cell proliferation, lipomatous tumour and mosaic KRAS mutation

Keratinocytic epidermal nevus syndrome (KENS) is a complex disorder not only characterized by the presence of epidermal nevi but also by abnormalities in the internal organ systems. A small number of cases with KENS are molecularly characterized and reported in the literature with somatic activating RAS, FGFR3 and PIK3CA mutations.status: publishe

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum: A brief report

A patient with extensive multisystem overgrowth caused by a somatic gain of function PIK3CA-mutation is described. This case is an example of the clinical diversity of the PIK3CA-Related Overgrowth Spectrum (PROS) as the patient had overlapping features of Congenital Lipomatous Overgrowth Vascular malformations Epidermal nevi and Skeletal abnormalities (CLOVES) syndrome and Megalencephaly-Capillary malformation Polymicrogyria (MCAP) syndrome and underlines the utility of this umbrella term.status: publishe

Recurrent multilocular mandibular giant cell granuloma in neurofibromatosis type 1: Evidence for second hit mutation of NF1 gene in the jaw lesion and treatment with curettage and bone substitute materials

Giant cell granuloma (GCG) of the jaw is a rare, well-known feature of neurofibromatosis type 1 (NF1), an inborn multisystem disorder. Recently, the development of GCG in NF1 was attributed to second hit mutations in the NF1 gene. The treatment of GCG is pragmatic with a preference for local curettage of lytic osseous areas. This report describes the surgical therapy of an NF1-affected female with multilocular mandibular GCG and hypodontia who additionally suffered from a brain tumour and Hashimoto's thyroiditis. Although local recurrence of GCG was noted, augmentation of the curetted cavities with a bone substitute in successive interventions successfully restored the extensive periradicular local defects and stabilised the teeth. A meticulous in vitro study of the GCG specimen revealed a second hit mutation in the NF1 gene in the GCG spindle-cells. This study contributes to the increasing knowledge of the molecular basis for GCG in the jaw of NF1 patients, indicating that it is a neoplasm.publisher: Elsevier articletitle: Recurrent multilocular mandibular giant cell granuloma in neurofibromatosis type 1: Evidence for second hit mutation of NF1 gene in the jaw lesion and treatment with curettage and bone substitute materials journaltitle: Journal of Cranio-Maxillofacial Surgery articlelink: http://dx.doi.org/10.1016/j.jcms.2016.05.010 content_type: article copyright: © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.status: publishe

Analysis of microsatellite instability in gastric mucosa-associated lymphoid tissue lymphoma

In Helicobacter pylori gastritis, constant antigenic stimulation triggers a sustained B-cell proliferation. Errors made during this continuous DNA replication are supposed to be corrected by the DNA mismatch repair mechanism. Failure of this mismatch repair mechanism has been described in hereditary non-polyposis colorectal cancer (HNPCC) and results in a replication error phenotype. Inherent to their instability during replication, microsatellites are the best markers of this replication error phenotype. We aimed to evaluate the role of defects in the DNA mismatch repair (MMR) mechanism and microsatellite instability (MSI) in relation to the most frequent genetic anomaly, translocation t(11;18)(q21;q21), in gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we examined 10 microsatellite loci (BAT25, BAT26, D5S346, D17S250, D2S123, TGFB, BAT40, D18S58, D17S787 and D18S69) for instability in 28 patients with MALT lymphomas. In addition, these tumors were also immunostained for MLH1, MSH2, MSH6 and PMS2, as well as screened for the presence of t(11;18)(q21;q21) by real-time polymerase chain reaction (RT-PCR). We found MSI in 5/28 (18%) lymphomas, with MSI occurring in both t(11;18)(q21;q21)-positive and -negative tumors. One tumor displayed high levels of instability, and, remarkably, this was the only case displaying features of a diffuse large B-cell lymphoma. All microsatellite unstable lymphomas showed a loss of MSH6 expression. In conclusion, our data suggest that a MMR-defect may be involved in the development of gastric MALT lymphomas, and that a defect of MSH6 might be associated with those MSI-driven gastric lymphomas.status: publishe