Claes G Tropé

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

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Publications (103)436.59 Total impact

  • 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: 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
  • 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: 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: The stem cell factor (SCF) receptor CD117 (c-kit), is widely used for identification of hematopoietic stem cells and cancer stem cells. Moreover, CD117 expression in carcinoma cells indicates a poor prognosis in a variety of cancers. However the potential expression in tumor microenvironment and the biological and clinical impact are currently not reported. The expression of CD117 was immunohistochemically evaluated in a serial of 242 epithelial ovarian cancer (EOC) cases. Thirty-eight out of 242 cases were CD117 positive in fibroblast-like stromal cells and 22 cases were positive in EOC cells. Four cases were both positive in fibroblast-like stromal cells and EOC cells for CD117. CD117 expression in fibroblast-like stromal cells in ovarian carcinoma was closely linked to advanced FIGO stage, poor differentiation grade and histological subtype (p<0.05), and it was significantly associated with poor overall survival (OS) and progression free survival (PFS) (Kaplan-Meier analysis; p<0.05, log-rank test). CD117 expression in ovarian carcinoma cells was not associated with these clinicopathological variables. The CD117 positive fibroblast-like stromal cells were all positive for mesenchymal stem/stromal cell (MSC) marker CD73 but negative for fibroblast markers fibroblast activation protein (FAP) and α smooth muscle actin (α-SMA), indicating that the CD117+/CD73+ fibroblast-like stromal cells are a subtype of mesenchymal stem cells in tumor stroma, although further characterization of these cells are needed. It is concluded herewith that the presence of CD117+/CD73+ fibroblast-like stromal cells in ovarian carcinoma is an unfavorable clinical outcome indication.
    PLoS ONE 01/2014; 9(11):e112209. · 3.53 Impact Factor
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    ABSTRACT: Increased vascularity is a crucial event in the tumor progression and has prognostic significance in various cancers. However, the ultimate role of angiogenesis in the pathogenesis and clinical outcome of vulvar carcinoma patients is still not settled. Tumor vascularity using CD34 stained slides measured by Chalkley counting method as well as hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) immunoexpression was examined in 158 vulvar squamous cell carcinomas. Associations between vascular Chalkley count, HIF-1alpha and VEGF expression and clinicopathological factors and clinical outcome were evaluated. High CD34 Chalkley count was found to correlate with larger tumor diameter (P = 0.002), deep invasion (P < 0.001) and HIF-1alpha (P = 0.04), whereas high VEGF expression correlate significantly with poor tumor differentiation (P = 0.007). No significant association between CD34 Chalkley counts and VEGF expression and disease-specific survival was observed. High HIF-1alpha expression showed better disease specific survival in both univariate and multivariate analyses (P = 0.001). A significant association between high tumor vascularity and larger tumor size as well as deeper tumor invasion suggests an important role of angiogenesis in the growth and progression of vulvar carcinomas. HIF-1alpha expression in vulvar carcinomas was a statistically independent prognostic factor.
    BMC Cancer 10/2013; 13(1):506. · 3.33 Impact Factor
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    ABSTRACT: This follow-up of a randomized study was conducted to assess the long-term effects of external beam radiation therapy (EBRT) in the adjuvant treatment of early-stage endometrial cancer. Between 1968 and 1974, 568 patients with stage I endometrial cancer were included. After primary surgery, patients were randomly assigned to either vaginal radium brachytherapy followed by EBRT (n = 288) or brachytherapy alone (n = 280). Overall survival was analyzed by using the Kaplan-Meier method. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs. We also conducted analyses stratified by age groups. After median 20.5 years (range, 0 to 43.4 years) of follow-up, no statistically significant difference was revealed in overall survival (P = .186) between treatment groups. However, women younger than age 60 years had significantly higher mortality rates after EBRT (HR, 1.36; 95% CI, 1.06 to 1.76) than the control group. The risk of secondary cancer increased after EBRT, especially in women younger than age 60 years (HR, 2.02; 95% CI, 1.30 to 3.15). We observed no survival benefit of external pelvic radiation in early-stage endometrial carcinoma. In women younger than age 60 years, pelvic radiation decreased survival and increased the risk of secondary cancer. Adjuvant EBRT should be used with caution, especially in women with a long life expectancy.
    Journal of Clinical Oncology 09/2013; · 18.04 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
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    ABSTRACT: BACKGROUND: Vulvar squamous cell carcinoma is a cancer form with increasing incidence rate and few treatment options. Wee1 is a central regulator of the G2/M DNA-damage checkpoint, and has in previous studies been described as a prognostic biomarker and a potential target for therapy in other cancer forms. METHODS: In the present study we analyzed the expression of Wee1 in a panel of 297 vulvar tumors by immunohistochemistry. Furthermore, siRNA transfections were carried out in two vulvar cancer cell lines (SW-954 and CAL-39) in order to study the effect on cell cycle distribution (flow cytometry) and proteins (western blot) involved in DNA damage response and apoptosis. RESULTS: Wee1 kinase is increased in vulvar squamous cell carcinomas, as compared to expression in normal epithelium, and a high Wee1 expression is associated with markers of malignancy, such as lymph node metastasis and poor differentiation. Our in vitro results showed that siRNA mediated Wee1 silencing only led to a modest reduction in viability, when examined in vulvar cancer cell lines. Nonetheless, a marked increase in DNA damages, as assessed by augmented levels of gamma-H2AX, was observed in both cell lines in the absence of Wee1. CONCLUSIONS: Our results suggest that Wee1 may be involved in the progression of vulvar carcinomas. Based on our in vitro results, Wee1 is unlikely to function as a target for mono-treatment of these patients.
    BMC Cancer 06/2013; 13(1):288. · 3.33 Impact Factor
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    ABSTRACT: OBJECTIVE: HOX proteins are key transcription factors in embryogenesis. HOXB5 and HOXB8 were previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to breast carcinoma using gene expression arrays. The present study investigated the clinical role of HOXB5 and HOXB8 in advanced-stage (FIGO III-IV) ovarian serous carcinoma. METHODS: HOXB5 and HOXB8 protein expression was analyzed in 286 effusions and 76 patient-matched solid lesions (27 primary carcinomas, 49 metastases) using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival. RESULTS: Cytoplasmic HOXB5 protein was detected in 268/286 (94%) effusions. HOXB8 was expressed at both the cytoplasm (252/286; 88%) and nucleus (131/286; 46%) of carcinoma cells. Cytoplasmic HOXB5, cytoplasmic HOXB8 and nuclear HOXB8 were found in 56/76 (74%), 76/76 (100%) and 30/76 (39%) solid lesions, respectively, with significantly higher HOXB5 expression in effusions (p=0.002) and higher cytoplasmic HOXB8 in solid lesions (p<0.001). HOXB5 expression was higher in post-chemotherapy disease recurrence effusions compared to pre-chemotherapy effusions tapped at diagnosis (p=0.04). In univariate survival analysis of the effusion cohort, higher expression of cytoplasmic HOXB8 was associated with significantly shorter progression-free survival (p=0.033), whereas higher nuclear HOXB8 expression was associated with significantly shorter overall survival in analysis limited to patients with post-chemotherapy effusions (p=0.036). Neither finding was independent prognostic factor in Cox multivariate analysis. CONCLUSIONS: HOXB5 and HOXB8 are frequently expressed in ovarian serous carcinoma, with anatomic site-related differences for cytoplasmic staining. HOXB5 may be affected by chemotherapy in effusions. HOXB8 expression is associated with shorter survival in metastatic serous carcinoma.
    Gynecologic Oncology 02/2013; · 3.93 Impact Factor
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    ABSTRACT: Little is known about the genomic abnormalities of squamous cell carcinomas (SCC) of the vulva and how they correlate with gene expression. We determined the genomic and expression profiles of 15 such SCC using karyotyping, DNA ploidy analysis, arrayCGH, and expression arrays. Four of the five cases with clonal chromosomal aberrations found by G-banding showed highly abnormal karyotypes with multiple rearrangements. The imbalances scored by arrayCGH mapped to different chromosomes with losses being more common than gains. Frequent losses were scored from 3p and 8p whereas gains were frequent from 3q and 8q (loss of 8p with concomitant gain of 8q mostly occurred via 8q isochromosome formation). This is the first study of vulvar tumors using arrayCGH, and some frequent imbalances could be defined precisely. Of particular note were the sometimes large, sometimes small deletions of 3p and 9p which had minute areas in 3p14 and 9p23 as minimal commonly deleted regions. FHIT (3p14) and PTPRD (9p23) are the only genes here. They were both lost in seven cases, including homozygous losses of PTPRD in four tumors. Using qPCR we could demonstrate deregulation of the FHIT gene in tumor cells. Hence, this gene is likely to play a pathogenetic role in vulvar SCC tumorigenesis. Expression array analyses also identified a number of other genes whose expression profile was altered. Notable among the downregulated genes were MAL (in 2q11), KRT4 (in 12q13), and OLFM4 (in 13q14), whereas upregulated genes included SPRR2G (in 1q21.3) and S100A7A (in 1q21.3). © 2013 Wiley-Liss,Inc.
    Genes Chromosomes and Cancer 02/2013; · 3.55 Impact Factor
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    ABSTRACT: The cyclin-dependent kinase inhibitors p15(INK4b) and p57(KIP2) are important regulators of the cell cycle, and their abnormal expression has been detected in various tumors. However, little is known about the role of p15(INK4b) and p57(KIP2) in the pathogenesis of vulvar carcinoma, and the prognostic impact is still unknown. In our current study, we examined the expression of p15(INK4b) and p57(KIP2) in a large series of vulvar squamous cell carcinomas to elucidate the prognostic impact. Expression of p15(INK4b) and p57(KIP2) were examined in 297 vulvar squamous cell carcinomas using immunohistochemistry. Both uni- and multivariate analysis of prognostic factors were performed, and correlations with clinicopathologic parameters were examined. Compared to the high levels of p15(INK4b) and p57(KIP2) in normal vulvar squamous epithelium, low levels of p15(INK4b) and p57(KIP2) were found in 82% and 44% of vulvar carcinomas, respectively. Low levels of p15(INK4b) and p57(KIP2) correlated significantly with malignant features, including large tumor diameter (p = 0.03 and p = 0.001, respectively) and increased invasiveness (p = 0.003 and p = 0.04, respectively). Although p15(INK4b) and p57(KIP2) levels could not be identified as prognostic markers, combined analysis of p14(ARF)/p15(INK4b)/p16(INK4a) showed that patients whose tumors expressed low levels of two or three of these INK4 proteins had a worse prognosis than those with only low levels of one or no protein (univariate analysis p = 0.02). The independent prognostic significance of these INK4 proteins was confirmed by multivariate analysis (p = 0.008). We show for the first time that p15(INK4b) and p57(KIP2) may be involved in the progression of vulvar carcinomas and the combined p14(ARF)/p15(INK4b)/p16(INK4a) status was a statistically independent prognostic factor.
    PLoS ONE 01/2013; 8(4):e61273. · 3.53 Impact Factor
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    ABSTRACT: Sex hormone-binding globulin (SHBG) is known as a carrier protein. It is classically thought to be mainly synthesized in the liver and then secreted into the circulating system, where it binds to sex steroids with a high affinity and modulates the bio-availability of the hormones. Other organs known to produce SHBG include brain, uterus, testis, prostate, breast and ovary, and the local expressed SHBG may play an important role in tumor development. However, SHBG expression status and its clinicopathological significance in ovarian cancer cells are not reported yet. In our present study, we examined and found the variable SHBG expression in four ovarian cancer cell lines (OV-90, OVCAR-3, SKOV-3 and ES-2) by immunocytochemistry and Western blotting. We then extended our study to 248 ovarian carcinoma samples, which were collected at The Norwegian Radium Hospital, Oslo University Hospital with complete clinical information, and discovered that SHBG was variably expressed in these ovarian carcinomas. Higher level of SHBG expression was significantly associated with more aggressive histological subtype (p = 0.022), higher FIGO stage (p = 0.018) and higher histological grade (grade of differentiation, p = 0.020), although association between SHBG expression and OS/PFS was not observed. Our results demonstrate that ovarian cancer cells produce SHBG and higher SHBG expression in ovarian carcinoma is associated with unfavorable clinicopathological features.
    PLoS ONE 01/2013; 8(12):e83238. · 3.53 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the expression and clinical role of the aurora A and aurora B kinases in primary and metastatic serous ovarian carcinoma. AURKA and AURKB messenger RNA expression was investigated 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. Aurora A and aurora B protein expression by immunohistochemistry was additionally analyzed in 147 tumors. Messenger RNA and protein expression at different anatomical sites were studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. AURKA and AURKB messenger RNA and their protein product were demonstrated in all primary carcinomas, solid metastases, and effusions. The expression of AURKA messenger RNA and aurora A protein was higher in effusions compared with solid specimens (P = .003 and P = .006, respectively). AURKB messenger RNA expression was higher in primary carcinomas, and solid metastases obtained prechemotherapy compared with postchemotherapy (P < .001 and P = .012, respectively), with no such difference in effusions (P > .05). Low aurora B protein expression was associated with primary chemotherapy resistance (P = .006) and poor treatment response (P = .013) in prechemotherapy effusions. No significant association was found between messenger RNA levels or protein expression and progression-free or overall survival. The present study documents for the first time frequent aurora A and aurora B expression in metastatic ovarian carcinoma, suggesting a role in cancer progression, with higher aurora A expression in effusions compared with primary carcinomas and solid metastases. Low AURKB messenger RNA expression in prechemotherapy effusions might be predictive of intrinsic chemotherapy resistance.
    Human pathology 10/2012; · 3.03 Impact Factor

Publication Stats

2k Citations
436.59 Total Impact Points


  • 2006–2014
    • Oslo University Hospital
      • • Institute for Medical Informatics
      • • Department of Pathology
      • • Department of Medical Genetics
      Kristiania (historical), Oslo County, Norway
  • 2000–2014
    • University of Oslo
      • • Institute of Clinical Medicine
      • • Department of Pathology (PAT)
      • • Department of Medical Genetics (DMG)
      • • Department of Oral Biology
      Kristiania (historical), Oslo County, Norway
  • 2003–2012
    • Hebrew University of Jerusalem
      • • Institute for Drug Research
      • • School of Pharmacy
      Jerusalem, Jerusalem District, Israel
  • 2011
    • Hospital Bærum
      Drammen, Buskerud county, Norway
  • 2005
    • National Cancer Institute (USA)
      • Laboratory of Pathology
      Maryland, United States
  • 2004
    • Gynecologic Oncology Group
      Buffalo, New York, United States