Dominique Bellet

18F-FDG PET/CT imaging versus dynamic contrast-enhanced CT for staging and prognosis of inflammatory breast cancer

PurposeInflammatory breast cancer (IBC) is the most aggressive type of breast cancer with a poor prognosis. Locoregional staging is based on dynamic contrast-enhanced (DCE) CT or MRI. The aim of this study was to compare the performances of FDG PET/CT and DCE CT in locoregional staging of IBC and to assess their respective prognostic values.MethodsThe study group comprised 50 women (median age: 51u2009±u200911xa0years) followed in our institution for IBC who underwent FDG PET/CT and DCE CT scans (median interval 5u2009±u20099xa0days). CT enhancement parameters were net maximal enhancement, net early enhancement and perfusion.ResultsThe PET/CT scans showed intense FDG uptake in all primary tumours. Concordance rate between PET/CT and DCE CT for breast tumour localization was 92xa0%. No significant correlation was found between SUVmax and CT enhancement parameters in primary tumours (pu2009>u20090.6). PET/CT and DCE CT results were poorly correlated for skin infiltration (kappau2009=u20090.19). Ipsilateral foci of increased axillary FDG uptake were found in 47 patients (median SUV: 7.9u2009±u20095.4), whereas enlarged axillary lymph nodes were observed on DCE CT in 43 patients. Results for axillary node involvement were fairly well correlated (kappau2009=u20090.55). Nineteen patients (38xa0%) were found to be metastatic on PET/CT scan with a significant shorter progression-free survival than patients without distant lesions (pu2009=u20090.01). In the primary tumour, no statistically significant difference was observed between high and moderate tumour FDG uptake on survival, using an SUVmax cut-off of 5 (pu2009=u20090.7 and 0.9), or between high and low tumour enhancement on DCE CT (pu2009>u20090.8).ConclusionFDG PET/CT imaging provided additional information concerning locoregional involvement to that provided by DCE CT on and allowed detection of distant metastases in the same whole-body procedure. Tumour FDG uptake or CT enhancement parameters were not correlated and were not found to have any prognostic value.

Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells.

BACKGROUNDnThe sequence of the beta-subunit of human chorionic gonadotropin (hCGβ) varies depending on whether hCGβ is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCGβ can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCGβ encoded by type II genes (type II hCGβ).nnnMETHODSnCompetitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCGβ dosing immunoassays and sequencing of CGB genes were performed.nnnRESULTSnCompetitive inhibition assays determined that mAb FBT11-II recognizes the type II hCGβ derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and T24 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCGβ. Placenta immunohistochemical studies confirmed that type II hCGβ expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCGβ in serum of patients with either nontrophoblastic cancers or fetal Down syndrome.nnnCONCLUSIONnType II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

Molecular Imaging of Neuroendocrine Cancer by Fusion SPET/CT

Neuroendocrine (NE) cancers are usually suspected on clinical symptoms related to their metabolically active peptide secretion into the circulatory system. The most effective treatment is surgery and a preoperative accurate localization of these slow growing tumors is needed. Combined anatomical (CT) and molecular imaging modalities using single-photon emission computed tomography (SPET) with radiolabeled pentetreotide have been developed in routine, and we report here the potential of SPECT/CT image fusion for diagnosis, staging, and evaluation of treatment efficacy of NE cancers.

The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors

ABSTRACT The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis—while surviving hypoxia—, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood, as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition, immune response, and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B is a key hub. Taken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.

Abstract 2762: Common DNA methylation patterns in cancer and placental cells involved in migration and invasion, immune escape, and angiogenesis induction

Identifying common patterns of regulation in cancer and placental cells might shed new light on cellular programs allowing aggressive tumor development. Indeed, as it has been described for the first time more than a century ago, cancer and placental cells (trophoblasts) share astonishingly similar phenotypes : migration and invasion, immune escape, and angiogenesis induction. These common phenotypes, relying on common genomic sequences and transcriptomic profiles, may result from a shared epigenomic regulation program. This might be especially true for tumor cells leading eventually to metastasis and cytotrophoblasts (a trophoblasts subset) during placental implantation at the beginning of pregnancy. In order to investigate such common epigenomic patterns, we carried out comparisons of DNA methylation in cancer and placental cell genomes. This study involved: cancer samples (primary tumor vs. normal tissue) across various tissues (including breast, colon, liver, lung, prostate, thyroid, uterus), on one hand; and placenta samples (early vs. late term) either heterogeneous (chorionic villi) or homogenous (ex vivo cytotrophoblasts), on the other hand. Cancer data were data downloaded from The Cancer Genome Atlas web portal. Placenta data were downloaded from the Gene Expression Omnibus web portal. In addition, our group generated original data from ex vivo cytotrophoblasts samples. All data were generated on the Illumina Infinium 450K array. Data analysis was carried out thanks to computational methods for epigenomics recently described. This first direct comparison of cancer and placental cells epigenomes, leveraging both published data and original data, led to the identification of large hypomethylated blocks common to cancer and placental cells. Such common patterns have recently been described as a universal defining epigenetic alteration in human solid tumors. These megabase-scale DNA methylation marks differentiate primary tumors from normal tissues. Likewise, they differentiate early term placentas from late term placentas. Moreover, genes belonging to genomic regions displaying common large hypomethylated blocks overlapping in cancers and placentas are enriched for pathways involved in migration and invasion, immune escape, and angiogenesis induction. Common DNA methylation patterns in cancer and placental cells identified in this pilot study might contribute to the epigenomic regulation of cellular programs allowing aggressive tumor development. Further analyses of these common patterns, as well as analyses of differences in cancer and placental cell epigenomes, could eventually lead to the identification of critical epigenomic switches that prevent healthy placentas to degenerate into tumors, while they allow aggressive tumors to develop. Ultimately, such epigenomic switches could also represent innovative targets in oncology. Citation Format: Akpeli V. Nordor, Sophie Richon, Thierry Fournier, Dominique Bellet, Virginie Dangles-Marie, Martin J. Aryee. Common DNA methylation patterns in cancer and placental cells involved in migration and invasion, immune escape, and angiogenesis induction. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2762.