No abstract

The endothelium is one of the largest cellular compartments of the human body and has a high proliferative potential. However , angiosarcomas are among the rarest malignancies. Despite this interesting contradiction , data on growth and angiogenesis control mechanisms of angiosarcomas are scarce. In this study of 19 angiosarcomas and 10 benign vascular control lesions we investigated the sequence and expression of the p53 tumor suppressor gene and the expression of the mdm-2 proto-oncogene , which is a negative regulator of p53 activity and of the vascular endothelial growth factor (VEGF) , whose expression, among other factors , is regulated by the p53/MDM-2 pathway. Ten sarcomas (53%) exibited clear nuclear p53 protein accumulation. Two of these cases revealed mutations in the sequence-specific DNA binding domain of the p53 gene. Thirteen angiosarcomas (68%) showed an increased amount of MDM-2 protein. Elevated expression of p53 and MDM-2 protein correlated with increased VEGF expression , which was found in nearly 80% of the angiosarcoma cases. Negative or clearly lower immunostaining was obtained in cases from the benign control collective.

There is a need for predictive biomarkers that identify non-small-cell lung cancer (NSCLC) patients most likely to respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There are numerous potential candidates, although none has been proven in prospective clinical trials. The EGFR gene copy number evaluated by fluorescence in situ hybridisation (FISH) has been highlighted as one of the most effective markers for sensitivity to EGFR TKIs in large phase III, randomised placebo-controlled trials and has been used in clinical settings to assist physicians in defining the therapeutic regimen. The EGFR FISH assay has technical challenges and it is critical that detailed guidelines are provided to help clinical laboratories in performing and interpreting the test. Excellent assay reproducibility and portability rates among laboratories are crucial to guarantee that accurate clinical decisions can be made for patients with NSCLC. This article discusses the consensus outcomes of a global workshop convened to discuss key technical issues and standardise reading strategies for the EGFR FISH assay of NSCLC tumour tissue.

V emurafenib is active against metastatic melanoma with BRAF V600E mutation. 1,2 BRAF mutations were reported in 3% to 5% of non-small-cell lung cancers (NSCLC) by the US Lung Cancer Mutation Consortium and by Italian investigators. 3,4 In vitro, MEK inhibition in lung cancer cell lines with V600E induced apoptosis, but clinical experience with drugs targeting the RAS/RAF/MEK pathway in V600E-NSCLC is limited. 5 CASE REPORT An 80-year-old man was admitted to our hospital with a history of shortness of breath and hoarseness. He was a former smoker and received torasemide (a diuretic) for hypertensive heart disease. Computed tomography (CT) scan showed a central tumor in the left lung, mediastinal lymph node metastases, and left pleural effusion (Fig. 1A). Drainage of pleural and pericardial effusion was performed, followed by pericardial instillation of bleomycin and talc slurry of the left pleura. Cytology revealed thyroid transcription factor-1 positive cancer cells, consistent with the diagnosis of NSCLC stage M1a (Fig. 2A). Polymerase chain reaction and direct sequencing showed BRAF V600E mutation (Fig. 2B). Sequencing of epidermal growth factor receptor exon 18 to 21, KRAS exon 2, and human epidermal growth factor receptor 2 exon 19 to 20 was negative. Anaplastic lymphoma kinase fluorescence in situ hybridization was also negative. The performance status was 4, the prognosis was very poor, chemotherapy was not recommended, and the patient was ineligible for a clinical trial with an MEK inhibitor. After exclusion of contraindications, the patient was offered vemurafenib off-label use. Pretreatment fluorodeoxyglucose-positron emission tomography/CT was performed (Fig. 1B), vemurafenib was initiated at the regular dose of 960 mg bid, and the patient left the hospital in a stable condition supported by family and professional home care. After 1 week of vemurafenib, his clinical and laboratory parameters were stable, and he decided to continue.

The frequent demonstration of intraductal carcinoma indicates that this preinvasive lesion is likely to be a constant feature in the malignant transformation of PA to CEPA. It appears to be a feature of CEPA developing from both primary and recurrent PA. The combined immunohistochemical and genetic data show that 14/19 cases of CEPA and 11/15 cases with intraductal carcinoma showed genetic or morphological evidence of dysfunctional p53, indicating that this is an early event in malignant transformation.