Ben Davidson

Oslo University Hospital, Kristiania (historical), Oslo County, Norway

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Publications (269)976.92 Total impact

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    ABSTRACT: Multicystic mesothelioma is a rare disease of unknown etiology and pathogenesis. Nothing has been known about the cytogenetic and molecular genetic features of these tumors. Here we present the first cytogenetically analyzed multicystic mesothelioma with the karyotype 46,XX,t(7;17)(p13;q23),t(8;11)(q23;p13). RNA-sequencing showed that the t(7;17)(p13;q23) generated a chimeric TNS3-MAP3K3 gene, which codes for a chimeric protein kinase, as well as the reciprocal MAP3K3-TNS3 in which the region of TNS3 coding for the SH2_Tensin_like region and the tensin phosphotyrosine-binding domain is under the control of the MAP3K3 promoter. The other translocation, t(8;11)(q23;p13), generated a chimeric ZFPM2-ELF5 gene which codes for a chimeric transcription factor in which the first 40 amino acids of ELF5 are replaced by the first 100 amino acid of ZFPM2. RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcripts. The finding of acquired clonal chromosome abnormalities in cells cultured from the lesion and the presence of the TNS3-MAP3K3 chimeric protein kinase and the ZFPM2-ELF5 chimeric transcription factor confirm the neoplastic nature of multicystic mesothelioma. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Cancer letters. 12/2014;
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    ABSTRACT: We recently identified gene signatures which allow classification of ovarian carcinoma into 5 distinct clinically-relevant groups. In the present study, we investigated the clinical role of 10 protein products of the discriminating genes, with focus on epithelial-mesenchymal transition and stem cell markers. Expression of E-cadherin, N-cadherin, P-cadherin, Zeb1, HMGA2, Rab25, CD24, NCAM (CD56), Sox11 and vimentin was assessed in 100 advanced-stage (FIGO III-IV) serous ovarian carcinoma effusions using immunohistochemistry. Results were analyzed for association with clinicopathologic parameters, including chemotherapy response, and survival. All 10 proteins were frequently expressed in carcinoma cells. HMGA2 expression was related to older age (p = 0.015). HMGA2 and NCAM expression was related to stage III disease (p = 0.011 and p = 0.023, respectively) and NCAM was overexpressed in peritoneal compared to pleural effusions (p = 0.001). Vimentin and Zeb1 expression was significantly related to poor chemotherapy response at diagnosis (p = 0.005 and p = 0.017, respectively). The associations between NCAM and peritoneal localization and of vimentin and poor chemoresponse were retained after Bonferroni correction. NCAM expression was associated with a trend for shorter overall survival in univariate survival analysis (p = 0.187), but emerged as independent prognosticator in Cox multivariate analysis (p = 0.042). This study identifies Vimentin and Zeb1 as markers of poor chemoresponse in metastatic serous ovarian carcinoma effusions and suggests NCAM as potential prognostic marker in metastatic disease. The generally limited prognostic role of the studied markers emphasizes the difficulty in applying data obtained in studies of primary ovarian carcinomas to analyses of ovarian carcinoma effusions, reflecting the unique biology of the latter.
    Human pathology 10/2014; · 3.03 Impact Factor
  • Ben Davidson, Claes G Tropé
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    ABSTRACT: Ovarian cancer remains the most lethal gynecologic malignancy, owing to late detection, intrinsic and acquired chemoresistance and remarkable heterogeneity. Despite optimization of surgical and chemotherapy protocols and initiation of clinical trials incorporating targeted therapy, only modest gains have been achieved in prolonging survival in this cancer. This review provides an update of recent developments in our understanding of the etiology, origin, diagnosis, progression and treatment of this malignancy, with emphasis on clinically relevant genetic classification approaches. In the authors' opinion, focused effort directed at understanding the molecular make-up of recurrent and metastatic ovarian cancer, while keeping in mind the unique molecular character of each of its histological types, is central to our effort to improve patient outcome in this cancer.
    Women's health (London, England). 09/2014; 10(5):519-33.
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    ABSTRACT: Wee1-like kinase (Wee1) is a tyrosine kinase which negatively regulates entry into mitosis at the G2 to M-phase transition and has a role in inhibition of unscheduled DNA replication in S-Phase. The present study investigated the clinical role of Wee1 in advanced-stage (FIGO III-IV) ovarian serous carcinoma.
    Gynecologic oncology. 08/2014;
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    ABSTRACT: We previously described the overexpression of APOA1 and GPX3 in ovarian/peritoneal serous carcinoma compared with breast carcinoma effusions using gene expression array analysis. The objective of the present study was to validate this finding and to analyze the association between these genes and clinicopathologic parameters, including survival, in advanced-stage ovarian serous carcinoma.
    American Journal of Clinical Pathology 07/2014; 142(1):51-7. · 2.88 Impact Factor
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    ABSTRACT: The objective of this study was to analyze the expression, biological role and clinical relevance of exosomal microRNAs (miRNAs) from ovarian carcinoma effusion supernatants. Exosomal miRNA expression profiling was performed using miRNA Taqman arrays. Selected miRNAs were validated using quantitative PCR in 86 ovarian carcinoma effusion supernatants. The role of exosomal microRNA in this cancer was further studied using in vitro and in vivo models. miRNA profiling identified 99 miRNAs with high expression levels in exosomes from ovarian carcinoma effusion supernatants. Quantitative PCR validation of 11 miRNAs showed significant associations with effusion site (peritoneum vs. pleura) and FIGO stage. In univariate survival analysis, high levels of miRNAs 21, 23b and 29a were associated with poor progression-free survival (p=0.01, p=0.015 and p=0.009, respectively), whereas high expression of miRNA 21 correlated with poor overall survival (p=0.017). The latter association was retained in Cox multivariate analysis (p=0.001). Exposure of LP9 mesothelial cells and ES2 ovarian carcinoma cells to ovarian carcinoma effusion-derived exosomes inhibited tumor spheroid expansion and reduced mesothelial clearance area. Treatment of SCID mice with exosomes from ovarian carcinoma effusions prior to injection of tumor cells was associated with larger tumor load, more infiltrative tumors and shorter survival. Patient-derived ovarian carcinoma effusion exosomes contain multiple miRNAs, of which some may have clinical relevance. In experimental models, ovarian carcinoma exosomes affect both tumor cells and cells in the tumor microenvironment, and induce more aggressive disease. Collectively, these data demonstrate the central role of miRNAs and their content in the biology of this cancer.
    Carcinogenesis 06/2014; · 5.64 Impact Factor
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    ABSTRACT: It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory.
    BMC Cancer 05/2014; 14(1):315. · 3.33 Impact Factor
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    ABSTRACT: The objective of this study was to investigate the expression and clinical role of the spindle checkpoint kinase budding uninhibited by benzimidazole 1 (Bub1) in primary and metastatic advanced-stage ovarian serous carcinoma. BUB1 mRNA expression was analyzed in 178 tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144 patients with advanced-stage disease using quantitative real-time polymerase chain reaction (PCR). Bub1 protein expression by Western blotting was studied in 63 carcinomas (30 effusions and 33 solid lesions). BUB1 mRNA expression at different anatomic sites was studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. BUB1 mRNA was universally expressed in serous carcinomas, irrespective of anatomic site. BUB1 mRNA levels were uniformly low in six ovarian surface epithelium specimens analyzed for comparative purposes. Bub1 protein was expressed in 22/30 effusions and 28/33 solid lesions. BUB1 mRNA expression was significantly higher in chemo-naïve primary carcinomas and solid metastases compared to specimens obtained following neoadjuvant chemotherapy (p < 0.001) and was unrelated to chemotherapy exposure in effusions nor to chemoresponse or survival at any anatomic site. BUB1 mRNA levels in both effusions and solid lesions were strongly related to the mRNA levels of AURKA and AURKB previously studied in this cohort (p < 0.001 for both). Bub1 is widely expressed in primary and metastatic OC, suggesting a biological role in this cancer. BUB1 mRNA levels are lower following chemotherapy exposure in solid lesions, though its presence is unrelated to clinical behavior including response to chemotherapy and survival. BUB1 is co-expressed with AURKA and AURKB suggesting biological relationship between these spindle cell components.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2014; · 2.68 Impact Factor
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    ABSTRACT: The kinase Mnk2 is a substrate of the MAPK pathway and phosphorylates the translation initiation factor eIF4E. In humans, MKNK2, the gene encoding for Mnk2, is alternatively spliced yielding two splicing isoforms with differing last exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it. We found that the Mnk2a isoform is downregulated in breast, lung, and colon tumors and is tumor suppressive. Mnk2a directly interacts with, phosphorylates, activates, and translocates p38α-MAPK into the nucleus, leading to activation of its target genes, increasing cell death and suppression of Ras-induced transformation. Alternatively, Mnk2b is pro-oncogenic and does not activate p38-MAPK, while still enhancing eIF4E phosphorylation. We further show that Mnk2a colocalization with p38α-MAPK in the nucleus is both required and sufficient for its tumor-suppressive activity. Thus, Mnk2a downregulation by alternative splicing is a tumor suppressor mechanism that is lost in some breast, lung, and colon tumors.
    Cell Reports 04/2014; · 7.21 Impact Factor
  • Ben Davidson, Claes G Tropé, Reuven Reich
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    ABSTRACT: MicroRNAs (miRNAs, miRs) are non-coding RNAs which post-transcriptionally regulate mRNA synthesis. Data regarding the expression and clinical relevance of miRNAs and the miRNA-regulating machinery in ovarian carcinoma has been rapidly expanding in recent years. This review presents current knowledge in this area. PubMed search was undertaken using the terms 'ovarian' and 'microRNA' RESULTS: A total of 492 papers were identified, of which approximately 100 were publications in English focusing exclusively or partly on clinical ovarian carcinoma specimens. These studies have identified multiple miRNAs with a potential role in the diagnosis, biology and progression of ovarian carcinoma, as well as on predicting chemoresponse and determining prognosis. The presented data support a clinical role for miRNAs in ovarian carcinoma and suggest that miRNA-regulated pathways may be of relevance for novel therapeutics. Novel technologies offer new possibilities for wide-scale miRNA-based classification of OC. Further genomic research focusing on larger series of tumors of similar histological type in combination with experimental approaches is likely to expand our understanding of the role of miRNAs in this cancer.
    Gynecologic Oncology 04/2014; · 3.93 Impact Factor
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    ABSTRACT: Chromosome 19 is frequently rearranged in ovarian carcinomas, but the pathogenetic consequences of this are not clearly understood. We performed microarray gene expression analysis on 12 ovarian carcinomas that carry a rearranged chromosome 19 in their karyotype. These aberrant chromosomes have previously been microdissected and analyzed by array-based CGH. In the current study, we wanted to explore whether the genomic alterations thus detected correlated with changes in gene expression. The microarray gene expression analysis gave information on 407 genes mapping in gained genomic regions on chromosome 19, of which 92 showed association between DNA gain and upregulated expression. Of the genes showing this association, 39 (42%) showed gain in at least two samples. The majority of these 39 genes of interest (n = 24, 62%) encode zinc finger proteins, which otherwise make up only 15% of the approximately 1,400 genes on chromosome 19. The strongest association was found for ZNF223 which was upregulated in samples with genomic gain compared with samples without gain. We suggest that DNA copy number changes brought about by rearrangements of chromosome 19 contribute to ovarian carcinogenesis by leading to upregulation of ZNF223 and other zinc finger genes. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 03/2014; · 3.55 Impact Factor
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    ABSTRACT: Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions. Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously. Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC. Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these miRNAs. miR-200 family members, targeting EMT drivers, were mostly overexpressed in both subgroups, among which miR-200c-3p was associated with survival in HGSC patients. A set of miRNAs differentiates CCC from HGSC, of which miR-509-3-5p and miR-509-5p are the strongest classifiers. Several interactions between miRNAs and mRNAs in HGSC were mapped.
    BMC Cancer 02/2014; 14(1):80. · 3.33 Impact Factor
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    ABSTRACT: The chimeric transcripts described in endometrial stromal sarcomas (ESS) are JAZF1/SUZ12, YWHAE/FAM22, ZC3H7/BCOR, MBTD1/CXorf67, and recombinations of PHF1 with JAZF1, EPC1, and MEAF6. The MEAF6/PHF1 fusion had hitherto been identified in only one tumor. We present two more ESS with MEAF6/PHF1 detected by transcriptome sequencing (case 1) and RT-PCR (case 2), proving that this fusion is recurrent in ESS. The transcript of both cases was an in-frame fusion between exon 5 of MEAF6 and exon 2 of PHF1. Both genes are involved in epigenetic modification, and this may well be their main pathogenetic theme also in ESS tumorigenesis.
    Cancer letters 02/2014; · 5.02 Impact Factor
  • Xavier Matias-Guiu, Ben Davidson
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    ABSTRACT: This article reviews the main prognostic and predictive biomarkers of endometrial (EC) and ovarian carcinoma (OC). In EC, prognosis still relies on conventional pathological features such as histological type and grade, as well as myometrial or lymphovascular space invasion. Estrogen receptor, p53, Ki-67, and ploidy analysis are the most promising biomarkers among a long list of molecules that have been proposed. Also, a number of putative predictive biomarkers have been proposed in molecular targeted therapy. In OC, prognosis is predominantly dependent on disease stage at diagnosis and the extent of residual disease at primary operation. Diagnostic markers which aid in establishing histological type in OC are available. However, not a single universally accepted predictive or prognostic marker exists to date. Targeted therapy has been growingly focused at in recent years, in view of the frequent development of chemoresistance at recurrent disease. The present review emphasizes the crucial role of correct pathological classification and stringent selection criteria of the material studied as basis for any evaluation of biological markers. It further emphasizes the promise of targeted therapy in EC and OC, while simultaneously highlighting the difficulties remaining before this can become standard of care.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2014; · 2.68 Impact Factor
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    ABSTRACT: The identification of recurrent gene fusions in common epithelial cancers-for example, TMPRSS2/ERG in prostate cancer and EML4/ALK in nonsmall cell lung carcinomas-has raised the question of whether fusion genes are pathogenetically important also in ovarian carcinomas. The first recurrent fusion transcript in serous ovarian carcinomas was reported by Salzman et al. in 2011, who used deep paired-end sequencing to detect the fusion gene ESRRA-C11orf20 in 10 out of 67 (15%) serous ovarian carcinomas examined, a finding that holds great promise for our understanding of ovarian tumorigenesis as well as, potentially, for new treatment strategies. We wanted to test how frequent the ESRRA/C11orf20 fusion is in ovarian carcinomas of all subtypes, and therefore examined a series of 230 ovarian carcinomas of which 197 were of the serous subtype and 163 of the 197 were of stages III and IV-that is, the very same carcinoma subset where the fusion transcript had been found. We performed PCR and high-throughput sequencing analyses in search of the fusion transcript. We used the same primers described previously for the detection of the fusion and the same primer combination, but found no ESRRA/C11orf20 fusion in our series. A synthetic DNA plasmid containing the reported ESRRA/C11orf20 fusion was included as a positive control for our PCR experiments. Data from high-throughput sequencing of 23 ovarian carcinomas were screened in search of alternative partner(s) for the ESRRA and/or C11orf20 gene, but none was found. We conclude that the frequency of the ESRRA/C11orf20 gene fusion in serous ovarian carcinomas of stages III and IV must be considerable less than that reported previously (0/163 in our experience compared with 10/67 in the previous study). At the very least, it seems clear that the said fusion cannot be a common pathogenetic event in this tumor type.
    PLoS Biology 02/2014; 12(2):e1001784. · 12.69 Impact Factor
  • Ben Davidson, Claes G Trope, Reuven Reich
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    ABSTRACT: The tumor microenvironment, consisting of stromal myofibroblasts, endothelial cells, and leukocytes, is growingly perceived to be a major contributor to the pathogenesis and disease progression in practically all cancer types. Stromal myofibroblasts produce angiogenic factors, proteases, growth factors, immune response-modulating proteins, anti-apoptotic proteins, and signaling molecules, and express surface receptors and respond to stimuli initiated in the tumor cells to establish a bi-directional communication network in the microenvironment to promote tumor cell invasion and metastasis. Many of these molecules are candidates for targeted therapy and the cancer stroma has been recently regarded as target for biological intervention. This review provides an overview of the biology and clinical role of the stroma in ovarian cancer.
    Frontiers in oncology. 01/2014; 4:104.
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    ABSTRACT: The involvement of VICKZ proteins has been implicated in a large number of cancers. The aim of the present study was to investigate the biological and clinical role of VICKZ proteins in ovarian carcinoma. VICKZ1-3 protein expression was analyzed in 82 serous ovarian carcinoma specimens (51 effusions, 14 primary carcinomas, 17 solid metastases) by immunoblotting. Protein localization was studied using immunohistochemistry in 101 tumors (40 effusions, 25 primary carcinomas, 36 solid metastases). The effect of VICKZ silencing using short hairpin RNA (shRNA) on collagenolytic activity and invasion was assessed in ES-2 ovarian carcinoma cells. VICKZ2 was the most frequently expressed family member in serous carcinomas. VICKZ levels measured by pan-VICKZ antibody were significantly higher in primary carcinomas and solid metastases compared to effusions (p<0.001). In contrast, VICKZ1 and VICKZ2 were overexpressed in effusions compared to primary carcinomas and solid metastases (p=0.016 and p=0.024, respectively), and higher VICKZ2 expression in effusions was associated with shorter overall survival in univariate analysis (p=0.01). All 3 proteins were localized to OC cells by immunohistochemistry, with tumor-specific expression observed for VICKZ1 and VICKZ2. VICKZ silencing in ES-2 cells led to reduced matrix metalloproteinase-9 activity and reduced invasion. In conclusion, VICKZ2 is the most frequently expressed VICKZ family member in serous ovarian carcinomas. VICKZ1 and VICKZ2 are overexpressed in effusions compared to primary carcinomas and solid metastases, suggesting a biological role at this anatomic site, and appear to have a role in proteolysis and invasion. VICKZ2 may be a prognostic marker in ovarian serous carcinoma effusions.
    Human pathology 01/2014; · 3.03 Impact Factor
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    ABSTRACT: Leiomyosarcoma (LMS) is the most common uterine sarcoma. Although the disease is relatively rare, it is responsible for considerable mortality due to frequent metastasis and chemoresistance. The molecular events related to LMS metastasis are unknown to date. The present study compared the global gene expression patterns of primary uterine LMSs and LMS metastases. Gene expression profiles of 13 primary and 15 metastatic uterine LMSs were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. To identify differently expressed genes between primary and metastatic tumors, we performed one-way analysis of variance with Benjamini-Hochberg correction. This led to identification of 203 unique probes that were significantly differentially expressed in the 2 tumor groups by greater than 1.58-fold with P < .01, of which 94 and 109 were overexpressed in primary and metastatic LMSs, respectively. Genes overexpressed in primary uterine LMSs included OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS, and TSPAN7. Genes overexpressed in LMS metastases included TNNT1, FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2, and AGT. Quantitative real-time PCR confirmed significant anatomical site-related differences in FOLR3, OSTN, and NLGN4X levels; and immunohistochemistry showed significant differences in TDO2 expression. Gene expression profiling differentiates primary uterine LMSs from LMS metastases. The molecular signatures unique to primary and metastatic LMSs may aid in understanding tumor progression in this cancer and in providing a molecular basis for prognostic studies and therapeutic target discovery.
    Human pathology 11/2013; · 3.03 Impact Factor
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    ABSTRACT: The objective of this study was to analyze the expression and clinical role of calreticulin, a multifunctional Ca(2+)-binding chaperone of the endoplasmic reticulum, in advanced-stage high-grade serous ovarian carcinoma. Cellular calreticulin messenger RNA (mRNA) and protein expression was investigated in 102 and 56 tumors, respectively, using reverse transcriptase polymerase chain reaction and Western blotting. Secreted calreticulin level was further analyzed in 31 effusion supernatants. Results were analyzed for association with anatomical site and clinicopathologic parameters, including survival. Calreticulin mRNA and protein were detected in 101 of 102 and 55 of 56 tumors, respectively. Calreticulin mRNA was overexpressed in solid metastases (n = 15) compared with effusions (n = 55) and primary carcinomas (n = 32; P = .009), whereas protein expression was significantly higher in solid metastases and primary carcinomas compared with effusion specimens (P = .007). Secreted calreticulin levels were higher in peritoneal compared with pleural effusions (P = .02). Higher cellular calreticulin protein expression in effusions was associated with better response to chemotherapy at diagnosis (P = .037). Calreticulin mRNA and protein expression was unrelated to patient survival. In conclusion, calreticulin is frequently expressed in serous ovarian carcinoma cells at all anatomical sites, but expression is reduced in effusions. Calreticulin protein levels in effusions may be predictive of chemotherapy response at diagnosis.
    Human pathology 09/2013; · 3.03 Impact Factor
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    ABSTRACT: Advanced-stage ovarian carcinoma is a highly lethal malignancy, yet no widely accepted prognostic panels exist to date in this disease. The objective of this study was to define such panel for patients with ovarian serous carcinoma effusions. The expression by immunohistochemistry and clinical role of 41 previously studied cancer-associated proteins was analyzed in 143 effusions from patients diagnosed as having advanced-stage (International Federation of Gynecology and Obstetrics stages III-IV) ovarian serous carcinoma treated with platinum-based chemotherapy at diagnosis. Survival analyses were performed separately for patients with prechemotherapy and postchemotherapy effusions. In univariate analysis of patients with primary diagnosis prechemotherapy effusions, survivin was associated with longer progression-free survival (P = .03), whereas survivin (P = .009), signal transducer and activator of transcription 5B (P = .011), and p21-activated kinase-1 (P = .04) were markers of longer overall survival. In univariate analysis of patients with disease recurrence postchemotherapy effusions, peroxisome proliferator-activated receptor-γ (P = .004), human leukocyte antigen-G (P = .013), mammalian target of rapamycin (P = .04), and nucleus accumbens 1 (NAC-1) (P = .046) were associated with poor progression-free survival, whereas peroxisome proliferator-activated receptor-γ (P = .013), claudin-3 (P = .019), activator protein-2γ (P = .04), insulin-like growth factor-2 (P = .04), claudin-7 (P = .042), and fatty acid synthase (P = .048) were markers of poor overall survival. In Cox multivariate analysis for prechemotherapy cases, survivin and fatty acid synthase were independent predictors of better progression-free survival (P = .006 and P = .048, respectively), and signal transducer and activator of transcription 5B and heat shock protein 90 were independently associated with better overall survival (P = .033 and P = .006, respectively). None of the biological markers was an independent prognostic factor in recurrent disease. The present study represents the first attempt at prognostic stratification of multiple tumor markers in one cohort of patients with ovarian serous carcinoma effusions.
    Human pathology 09/2013; · 3.03 Impact Factor

Publication Stats

5k Citations
976.92 Total Impact Points

Institutions

  • 2006–2014
    • Oslo University Hospital
      • • Department of Pathology
      • • Institute for Medical Informatics
      Kristiania (historical), Oslo County, Norway
  • 1999–2014
    • University of Oslo
      • • Department of Pathology (PAT)
      • • Faculty of Medicine
      Kristiania (historical), Oslo County, Norway
  • 2003–2013
    • Hebrew University of Jerusalem
      • • Institute for Drug Research
      • • School of Pharmacy
      • • Department of Pharmacology
      • • Faculty of Medicine
      Jerusalem, Jerusalem District, Israel
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2005–2012
    • National Cancer Institute (USA)
      • • Medical Oncology Branch and Affiliates
      • • Center for Cancer Research
      • • Laboratory of Pathology
      Maryland, United States
  • 1998–2012
    • Tel Aviv University
      • • Department of Pathology
      • • Department of Obstetrics and Gynecology
      Tel Aviv, Tel Aviv, Israel
  • 2011
    • University of Pittsburgh
      • Department of Pathology
      Pittsburgh, Pennsylvania, United States
  • 2007–2011
    • National Institutes of Health
      • • Laboratory of Cell Biology
      • • Center for Cancer Research
      Bethesda, MD, United States
  • 2005–2010
    • Johns Hopkins University
      • Department of Pathology
      Baltimore, MD, United States
    • Johns Hopkins Medicine
      • • Department of Gynecology & Obstetrics
      • • Department of Pathology
      Baltimore, MD, United States
  • 1997–2001
    • Sheba Medical Center
      • Department of Pathology
      Gan, Tel Aviv, Israel
  • 2000
    • Det Norske Veritas
      Kristiania (historical), Oslo County, Norway