ABSTRACT
Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.
Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Glioma/diagnosis , Glioma/genetics , Glioma/metabolism , Adult , Brain Neoplasms/classification , Chromosome Aberrations , Chromosome Deletion , Chromosomes, Human, Pair 1/genetics , ErbB Receptors/genetics , Female , Follow-Up Studies , Gene Expression Profiling , Glioma/classification , Humans , Isocitrate Dehydrogenase/genetics , Ki-67 Antigen/metabolism , Male , Middle Aged , Mutation/genetics , Necrosis , Oligonucleotide Array Sequence Analysis , Prognosis , Survival AnalysisABSTRACT
The aim of this study was to determine the frequency of EGFR, KRAS, BRAF, and HER-2 mutations in brain metastases from non-small cell lung carcinomas (BM-NSCLC). A total of 77 samples of BM-NSCLC were included and 19 samples of BM from breast, kidney, and colorectal tumors were also studied as controls. These samples were collected from patients followed between 2008 and 2011 at Poitiers and Nice University Hospitals in France. The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NSCLC were 2.6, 38.5, 0, and 0% respectively. The incidence of KRAS mutation was significantly higher in female and younger patients (P < 0.05). No mutations of the four genes were found in BM from breast or kidney. However, among six BM from colorectal tumors, we identified KRAS mutations in three cases and BRAF mutations in two other cases. This study is the largest analysis on genetic alterations in BM-NSCLC performed to date. Our results suggest a low frequency of EGFR mutations in BM-NSCLC whereas KRAS mutations are as frequent in BM-NSCLC as in primitive NSCLC. These results raise the question of the variability of the brain metastatic potential of NSCLC cells in relation to the mutation pattern.
Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Lung Neoplasms/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , Receptor, ErbB-2/genetics , ras Proteins/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Female , Genes, ras , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Proto-Oncogene Proteins p21(ras)ABSTRACT
AIMS: To evaluate by impression cytology (IC) the expression of the MHC class II inflammatory marker HLA-DR by the conjunctival epithelium, the cytological modifications of the conjunctival surface according to the Nelson's classification, and the eventual correlation between the two after severe ocular burns. METHODS: A total of 24 patients (24 eyes) who presented with severe ocular burns underwent IC. We compared them with 18 healthy eyes. HLA-DR expression was studied by flow cytometry as well as the conjunctival histology evaluated with the Nelson's classification from 2-24 months after the onset of burns. RESULTS: There was a significant upregulation of the expression of HLA-DR in eyes with burns compared to the healthy population at 2 months (p<0.001), 6 months (p<0.001), 12 months (p = 0.019), 18 months (p = 0.0171) and 24 months (p = 0.01766). A significant difference was found between the Nelson grade in the pathological population and those of the healthy population at 2 months (p = 0.0157). HLA-DR upregulation was significantly correlated with the Nelson's grades between 2 months (r = 0.69, p<0.0001) and 6 months (r = 0.61, p = 0.0001). CONCLUSION: The IC technique can act as a useful tool for following-up ocular surface inflammation after severe ocular burns.
