Molecular parameters associated with insulinoma progression: chromosomal instability versus p53 and CK19 status

Insulinomas represent the predominant syndromic subtype of endocrine pancreatic tumors (EPTs). Their metastatic potential cannot be predicted reliably using histopathological criteria. In the past few years, several attempts have been made to identify prognostic markers, among them TP53 mutations and immunostaining of p53 and recently cytokeratin 19 (CK19). In a previous study using conventional comparative genomic hybridization (CGH) we have shown that chromosomal instability (CIN) is associated with metastatic disease in insulinomas. It was our aim to evaluate these potential parameters in a single study. For the determination of CIN, we applied CGH to microarrays because it allows a high-resolution detection of DNA copy number changes in comparison with conventional CGH as well as the analysis of chromosomal regions close to the centromeres and telomeres, and at 1pter-->p32, 16p, 19 and 22. These regions are usually excluded from conventional CGH analysis, because they may show DNA gains in negative control hybridizations. Array CGH analysis of 30 insulinomas (15 tumors of benign, eight tumors of uncertain and seven tumors of malignant behavior) revealed that >or=20 chromosomal alterations and >or=6 telomeric losses were the best predictors of malignant progression. A subset of 22 insulinomas was further investigated for TP53 exon 5-8 gene mutations, and p53 and CK19 expression. Only one malignant tumor was shown to harbor an arginine 273 serine mutation and immunopositivity for p53. CK19 immunopositivity was detected in three malignant tumors and one tumor with uncertain behavior. In conclusion, our results indicate that CIN as well as telomeric loss are very powerful indicators for malignant progression in sporadic insulinomas. Our data do not support a critical role for p53 and CK19 as molecular parameters for this purpose

Molecular mechanism of extracutaneous tumours in patients with basal cell nevus syndrome

Basal cell nevus syndrome (BCNS) is a rare genetic disorder accompanied by a broad variety of tumours, of which basal cell carcinomas and odontogenic keratocysts are the most common. BCNS is caused by a germline or postzygotic mutation in either PTCH1 or SUFU As BCNS is a rare disease, it is difficult to establish whether less frequently occurring tumours are actually part of the syndrome. In this study, the molecular mechanism behind four extracutaneous tumours in patients with BCNS was elucidated. A leiomyoma of the testis and meningioma were confirmed to be associated with BCNS in two patients by presence of a second mutation or loss of heterozygosity in PTCH1 In a meningioma of a patient with a mosaic postzygotic PTCH1 mutation an association could not be conclusively confirmed. SUFU was probably not involved in the development of a thyroid carcinoma in a patient with a germline SUFU mutation. Hence, we have proven that meningioma and leiomyoma of the testis are rare extracutaneous tumours that are part of BCNS

Gain of chromosome 8q is a frequent finding in pleuropulmonary blastoma.

Contains fulltext : 53430.pdf (publisher's version ) (Closed access)Pleuropulmonary blastomas are rare malignant intrathoracic tumors of early childhood. They appear as a pulmonary- and/or pleural-based mass and their pathogenesis and relationship to other pediatric solid tumors is not well understood. In this study, paraffin-embedded material of five cases of pleuropulmonary blastoma was analyzed for genetic alterations by comparative genomic hybridization and five genetic loci by fluorescence in situ hybridization. Comparative genomic hybridization identified aberrations in all pleuropulmonary blastomas, including four amplifications in three tumors at chromosomes 5q33-34, 11q22.2-ter, 15q25-ter, and 19q11-13.2. The most frequent DNA gains involved 8q11-22.2 (four cases) and 20q (two cases), whereas the most common losses included 9p21-24 (two cases) and 11p14 (three cases). Chromosome 8 gains were confirmed by fluorescent in situ hybridization, resulting in the detection of up to five copies of chromosome 8 centromeres per nucleus. In the two surviving patients, chromosome 8 gains were the only genetic abnormality, suggesting that this might be an early event in pleuropulmonary blastoma carcinogenesis. The identification of new genetic alterations as well as the confirmation of previously reported ones (especially 8q gains) in pleuropulmonary blastoma should help to improve our understanding of both the molecular mechanisms underlying the tumorigenesis of pleuropulmonary blastoma and the relationship of pleuropulmonary blastoma with other pediatric tumors

Interobserver variability of laryngeal mucosal premalignant lesions: a histopathological evaluation.

Item does not contain fulltextThe objective of this study is to measure interobserver variability in the classification of laryngeal mucosal premalignant lesions by reassessing the histopathology of previously diagnosed cases and to determine the possible therapeutic consequences of disagreement among observers. Histopathological assessment of 110 laryngeal mucosal premalignant lesions was done by three pathologists. Each slide had to be classified according to the World Health Organization, Squamous Intraepithelial Neoplasia, and the Ljubljana Squamous Intraepithelial Lesions systems. After the independent assessment, a joint meeting took place. To assess the relation between histopathological grading and subsequent clinical management, we created a two- and a three-grade system besides one comprising all options. For all analyses, the SAS/STAT statistical software was used. The highest unweighted kappa-values concerning the all-options system are observed for the Squamous Intraepithelial Neoplasia classification (0.28, 95% confidence interval 0.23-0.33), followed by the World Health Organization and Ljubljana classifications. For the two-grade system the Ljubljana classification shows the highest unweighted kappa-values (0.50, 95%, 0.39-0.61), followed by the World Health Organization and Squamous Intraepithelial Neoplasia classifications. For the three-grade system, the unweighted kappa-values are similar. The implementation of weighted kappa-values led to higher scores within all three classification systems, although these did not exceed 0.55 (moderate agreement). Given the high level of consensus, simultaneous pathological assessment may be said to provide added value in comparison with independent assessment. In the current study, no clear tendency is observed in favor of any one classification system. The proposed three-grade system could be an improved histopathological tool because it is easier to correlate with clinical decision making and because it yields better unweighted kappa-values and proportions of concordance than the all-options system. Furthermore, clinical management could benefit from assessment by more than one pathologist in suspected cases of dysplasia or carcinoma.1 juli 201

Development of a non-destructive method for underglaze painted tiles – demonstrated by the analysis of Persian objects from the nineteenth century.

The paper presents an analytical method developed for the nondestructive study of nineteenth-century Persian polychrome underglaze painted tiles. As an example, 9 tiles from French and German museum collections were investigated. Before this work was undertaken little was known about the materials used in pottery at that time, although the broad range of colors and shades, together with their brilliant glazes, made these objects stand out when compared with Iranian ceramics of the preceding periods and suggested the use of new pigments, colorants, and glaze compositions. These materials are thought to be related to provenance and as such appropriate criteria for art-historical attribution. The analytical method is based on the combination of different nondestructive spectroscopic techniques using microfocused beams such as proton-induced X-ray emission/proton-induced γ-ray emission, X-ray fluorescence, 3D X-ray absorption near edge structure, and confocal Raman spectroscopy and also visible spectroscopy. It was established to address the specific difficulties these objects and the technique of underglaze painting raise. The exact definition of the colors observed on the tiles using the Natural Color System®© helped to attribute them to different colorants. It was possible to establish the presence of Cr- and U-based colorants as new materials in nineteenth-century Persian tilemaking. The difference in glaze composition (Pb, Sn, Na, and K contents) as well as the use of B and Sn were identified as a potential marker for different workshops