Tissue distribution and functional aspects of the NF2 tumour suppressor gene

Neoplastic disease in humans may occur sporadically, that is without a clear familial disposition, or less commonly as an inherited disease. Several distinct familial cancer syndromes are known and the underlying genetic cause has been identified of a number of these 46. The tumours in these syndromes are usually phenotypically identical to their sporadically occurring counterparts. Both syndromes with benign and with malignant tumours are known. In cancer syndromes tumours generally develop at a younger age than those seen in the non-familial setting and are often multiple 101. Most inherited cancer syndromes with an autosomal dominant inheritance pattern are caused by mutations in tumour suppressor genes. Far fewer inherited cancer syndromes are caused by mutations in (proto-)oncogenes, notably mUltiple endocrine neoplaSia type 2 and familial medullary thyroid cancer caused by mutations in the RET gene 99, 107, hereditary papillary renal cell carcinoma caused by mutations in the MET gene 124 and some cases of familial melanoma caused by mutations in the CDK4 gene 165. In addition to the classical tumour suppressor genes and proto-oncogenes, other genes involved in here

Mesenchymal tumours of the mediastinum—part II

This is the second part of a two-part review on soft tissue tumours which may be encountered in the mediastinum. This review is based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart and provides an updated overview of mesenchymal tumours that have been reported in the mediastinum

Histoplasma-associated inflammatory pseudotumour of the kidney mimicking renal carcinoma

A 56-year-old female, originally from Suriname, with an otherwise unremarkable previous medical history was found to have a renal mass highly suspicious for renal cancer for which a nephrectomy was performed. Within the kidney, a tumourous mass was found which, on histological examination, showed an inflammatory pseudotumour caused by Histoplasma capsulatum. Further investigations revealed an idiopathic CD4+ lymphopenia. Mass lesions mimicking a malignant tumour caused by infection with Histoplasma have rarely been described. To the best of our knowledge, this is the first report of a Histoplasma-associated inflammatory pseudotumour mimicking cancer occurring in the kidney

Time Trends in the Incidence and Treatment of Extra-Abdominal and Abdominal Aggressive Fibromatosis: A Population-Based Study

Background: Aggressive fibromatosis (AF) is a locally infiltrating soft-tissue tumor. In a population-based study in the Netherlands, we evaluated time trends for the incidence and treatment of AF. Methods: In PALGA: Dutch Pathology Registry, all patients diagnosed between 1993 and 2013 as having extra-abdominal or abdominal wall aggressive fibromatosis were identified and available pathology data of the patients were evaluated. Epidemiological and treatment-related factors were analyzed with χ2and regression analysis. Results: During the study period, 1134 patients were identified. The incidence increased from 2.10 to 5.36 per million people per year. Median age at the time of diagnosis increased annually by B 0.285 (P = 0.001). Female gender prevailed and increased over time [annual odds ratio (OR) 1.022; P = 0.058]. All anatomic localizations, but in particular truncal tumors, became more frequent. During the study period diagnostic histological biopsies were performed more often (annual OR 1.096; P < 0.001). The proportion of patients who underwent surgical treatment decreased (annual OR 0.928; P < 0.001). When resection was preceded by biopsy, 49.8 % of the patients had R0-resection versus 30.7 % in patients without biopsy (P < 0.001). Conclusions: In this population-based study, an increasing incidence of extra-abdominal and abdominal-wall aggressive fibromatosis was observed. The workup of patients improved and a trend towards a nonsurgical treatment policy was observed

Mesenchymal tumours of the mediastinum—part I

The mediastinum is an anatomically defined space in which organs and major blood vessels reside with surrounding soft tissue elements. The thymus is an important organ in the mediastinum, and many of the masses encountered in the mediastinum are related to this organ. Most neoplasms diagnosed in the mediastinum are epithelial tumours (thymomas and thymic carcinomas), lymphomas or germ cell tumours. In contrast, soft tissue tumours of the mediastinum are rare. In 1963, Pachter and Lattes systematically reviewed soft tissue pathology of the mediastinum, covering the hitherto described [2, 226, 227] In this review, based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart, we provide an updated overview of mesenchymal tumours that may be encountered in the mediastinum

Identification of a putative protein-profile associating with tamoxifen therapy-resistance in breast cancer

Tamoxifen-resistance is a major cause of death in patients with recurrent breast cancer. Current clinical parameters can correctly predict therapy response in only half of the treated patients. Identification of proteins that associate with tamoxifen-resistance is a first step towards better response prediction and tailored treatment of patients. In the present study we aimed to identify putative protein biomarkers indicative of tamoxifen therapy-resistance in breast cancer, using nanoLC-FTICR MS. Comparative proteome analysis was performed on ~5,500 pooled tumor cells obtained through laser capture microdissection from two independently processed data sets (n=24 and n=27) of tamoxifen therapy-sensitive and -resistant tumors. Peptide and protein identifications were acquired by matching mass and elution time features to information in previously generated accurate mass and time tag reference data bases. A total of 17,263 unique peptides were identified that corresponded to 2,556 non-redundant proteins identified with >=2 peptides. From this total, 1,713 protein

Tumor slice culture system to assess drug response of primary breast cancer

Background The high incidence of breast cancer has sparked the development of novel targeted and personalized therapies. Personalization of cancer treatment requires reliable prediction of chemotherapy responses in individual patients. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy. This selection can be facilitated by characterization of individual tumors using robust and specific functional assays, which requires development of powerful ex vivo culture systems and procedures to analyze the response to treatment. Methods We optimized culture methods for primary breast tumor samples that allowed propagation of tissue ex vivo. We combined several tissue culture strategies, including defined tissue slicing technology, growth medium optimization and use of a rotating platform to increase nutrient exchange. Results We could maintain tissue cultures for at least 7 days without losing tissue morphology, viability or cell proliferation. We also developed methods to determine the cytotoxic response of individual tumors to the chemotherapeutic treatment FAC (5-FU, Adriamycin [Doxorubicin] and Cyclophosphamide). Using this tool we designated tumors as sensitive or resistant and distinguished a clinically proven resistant tumor from other tumors. Conclusion This method defines conditions that allow ex vivo testing of individual tumor responses to anti-cancer drugs and therefore might improve personalization of breast cancer treatment

Gene expression-based classification of non-small cell lung carcinomas and survival prediction

Background: Current clinical therapy of non-small cell lung cancer depends on histo-pathological classification. This approach poorly predicts clinical outcome for individual patients. Gene expression profiling holds promise to improve clinical stratification, thus paving the way for individualized therapy. Methodology and Principal Findings:A genome-wide gene expression analysis was performed on a cohort of 91 patients. We used 91 tumor- and 65 adjacent normal lung tissue samples. We defined sets of predictor genes (probe sets) with the expression profiles. The power of predictor genes was evaluated using an independent cohort of 96 non-small cell lung cancer- and 6 normal lung samples. We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of non-small cell lung cancer. Correlation analysis identified 17 genes which showed the best association with post-surgery survival time. This signature was used for stratification of all patients in two risk groups. Kaplan-Meier survival curves show that the two groups display a significant difference in post-surgery survival time (p = 5.6E-6). The performance of the signatures was validated using a patient cohort of similar size (Duke University, n = 96). Compared to previously published prognostic signatures for NSCLC, the 17 gene signature performed well on these two cohorts. Conclusions:The gene signatures identified are promising tools for histo-pathological classification of non-small cell lung cancer, and may improve the prediction of clinical outcome

Chemotherapy for pulmonary large cell neuroendocrine carcinomas: Does the regimen matter?

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