Scopulariopsis species are rarely but increasingly recognized as opportunistic pathogens in immunocompromised patients. We report on a patient suffering from cystic fibrosis who developed disseminated fungal infection due to a rare Scopulariopsis species, Microascus cirrosus, after heart and lung transplantation. Despite antifungal combination therapy with voriconazole and caspofungin, the patient died 4 weeks after transplantation. Diagnostic difficulties and optimal management of disseminated Scopulariopsis/Microascus infections are discussed. CASE REPORTA 36-year-old man suffering from cystic fibrosis was admitted to our hospital in June 2009 for a heart and bilateral lung transplantation. He had a first lung transplantation in 1997 but had chronic rejection since 2001 in spite of several immunosuppressive regimens. His medical history also included renal failure (hemodialysis since 2007), diabetes mellitus, and airway colonization with a multiresistant Pseudomonas aeruginosa. Short antifungal therapy courses had been prescribed over the past years for various yeasts (Candida spp.) and molds (Aspergillus, Paecilomyces, and Fusarium species) colonizing his respiratory tract, but there was no evidence of previous isolation of a Scopulariopsis species. At the time of admission, sputum cultures grew only Candida albicans, and fluconazole was thus prescribed (200 mg intravenously [i.v.] after each dialysis).Following graft surgery, the immunosuppressive regimen included induction therapy with basiliximab (anti-CD25 antibody [20 mg i.v. on the day of transplantation and on day 4]) and solumedrol (10 mg/kg of body weight on the day of transplantation, followed by three 120-mg doses per day), followed by cyclosporine adjusted according to dialysis parameters to reach therapeutic blood levels (300 to 350 ng/ml) and solumedrol. Antimicrobial therapy consisted of a broad-spectrum antibiotherapy with tobramycin, vancomycin, piperacillin, and tazobactam. Although the patient seemed to do well in the early postoperative period, with apyrexia and extubation on day 3, his white blood cell count (WBC) increased slowly starting on the day after transplantation, reaching 20 ϫ 10 9 cells/liter by day 8 postsurgery. On day 11 after the operation (WBC ϭ 30 ϫ 10 9 cells/liter), a thoracic computed tomodensitometry (TDM) revealed bilateral pulmonary effusions (Fig. 1A), which were drained on day 19 without clinical improvement. Bilateral hemorrhagic pleural fluid specimens revealed several regular, hyaline, and branched septate hyphae on direct examination ( Fig. 2A), leading to the diagnosis of proven invasive fungal infection (IFI) according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria (8). The patient was given an antifungal combination therapy of voriconazole i.v. (6 mg/kg every 12 h as a loading dose followed by two 4-mg/kg doses a day) and caspofungin (70 mg/day ...

BACKGROUND:We recently identified and validated UBE2C RNA as a prognostic marker in 252 node-positive (N þ ) breast cancers by means of a microarray study. The aim of this study was to validate UBE2C protein as a prognostic marker in N þ breast cancer by immunohistochemistry (IHC). METHODS: To this end, 92 paraffin-embedded blocks were used. The impact of UBE2C IHC value on metastasis-free survival (MFS) and overall survival (OS) was evaluated and compared with Ki-67 and Nottingham prognostic index (NPI) performances. RESULTS: In accordance with genomic data, UBE2C IHC had a significant impact both on MFS and OS (hazard ratio ¼ 6.79 -P ¼ 0.002; hazard ratio ¼ 7.14 -P ¼ 0.009, respectively). Akaike information criterion proved that the prognostic power of UBE2C IHC was stronger than that of Ki-67 (and close to that of NPI). Furthermore, multivariate analyses with NPI showed that, contrary to Ki-67 IHC, UBE2C IHC remained an independent factor, both for MFS (adjusted P ¼ 0.02) and OS (adjusted P ¼ 0.04). CONCLUSION: We confirmed that UBE2C protein measured by IHC could be used as a prognostic marker in N þ breast cancer. The potential predictive interest of UBE2C as a marker of proteasome activity needs further investigations.

IDH1/2 mutations and 1p/19q codeletion occur frequently in anaplastic gliomas and are prognostic factors. We combined these two biomarkers to stratify patients treated for anaplastic oligodendroglioma (AO). 43 consecutive WHO AO were selected. We combined immunohistochemistry (IHC) with the monoclonal antibody mIDH1R132H and DNA sequencing of IDH1 and IDH2 genes. Fluorescence in situ hybridization was carried out to evaluate 1p/19q codeletion. These biomarkers were correlated with progression-free survival (PFS) and overall survival (OS). IDH1/IDH2 mutations occurred in 23/43 (54 %) patients: 20/43 IDH1-R132H mutation in IHC, 2/43 IDH1-R132G mutation and 1/43 IDH2-R172K mutation identified by DNA sequencing. 1p/19q codeletion was detected for 23/43 patients. With median follow-up of 19 months (range 1.4-128), median PFS and OS were 22 and 35 months respectively. IDH1/IDH2 mutations were strongly associated with improved PFS and OS: 5-year PFS was 86 versus 6 % and 5-year OS was 91 versus 9 % for patients with IDH1/IDH2 mutations versus wild-type IDH respectively. In multivariate analyses, IDH1/IDH2 mutations and 1p/19q loss were independent prognostic factors. Three groups with distinct prognostic features were identified: patients with IDH1/2 mutations and 1p/19q loss (median PFS, median OS not reached), patients with IDH1/2 mutations or 1p/19q loss (median PFS: 22 months, median OS: 30 months), and patients without IDH1/2 mutations nor 1p/19q loss with a bad prognosis (median PFS: 8.6 months, median OS: 9.9 months). Combining two biomarkers, IDH1/2 and 1p/19q codeletion, makes it possible to stratify AO in three groups with very distinct prognostic features.

E-cadherin immunostaining and HER1 in situ hybridisation define a group of well differentiated gastric carcinomas with poor prognosis eligible for an aggressive therapeutic approach.

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