Marick Laé

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (59)327.05 Total impact

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    ABSTRACT: Background: Hormone receptor status and HER2 status are of critical interest in determining the prognosis of breast cancer patients. Their status is routinely assessed by immunohistochemistry (IHC). However, it is subject to intra-laboratory and inter-laboratory variability. The aim of our study was to compare the estrogen receptor, progesterone receptor and HER2 status as determined by the MapQuant™ test to the routine immuno-histochemical tests in early stage invasive breast cancer in a large comprehensive cancer center. Patients and methods: We retrospectively studied 163 invasive early-stage breast carcinoma with standard IHC status. The genomic status was determined using the MapQuant™ test providing the genomic grade index. Results: We found only 4 tumours out of 161 (2.5%) with discrepant IHC and genomic results concerning ER status. The concordance rate between the two methods was 97.5% and the Cohen's Kappa coefficient was 0.89. Comparison between the MapQuant™ PR status and the PR IHC status gave more discrepancies. The concordance rate between the two methods was 91.4% and the Cohen's Kappa coefficient was 0.74. The HER2 MapQuant™ test was classified as « undetermined » in 2 out of 163 cases (1.2%). One HER2 IHC-negative tumour was found positive with a high HER2 MapQuant™ genomic score. The concordance rate between the two methods was 99.3% and the Cohen's Kappa coefficient was 0.86. Conclusion: Our results show that the MapQuant™ assay, based on mRNA expression assay, provides an objective and quantitative assessment of Estrogen receptor, Progesterone receptor and HER2 status in invasive breast cancer.
    No preview · Article · Feb 2016 · PLoS ONE
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    ABSTRACT: Background: Triple-negative breast cancers (TNBC) are a specific subtype of breast cancers with a particularly poor prognosis. However, it is a very heterogeneous subgroup in terms of clinical behavior and sensitivity to systemic treatments. Thus, the identification of risk factors specifically associated with those tumors still represents a major challenge. A therapeutic strategy increasingly used for TNBC patients is neoadjuvant chemotherapy (NAC). Only a subset of patients achieves a pathologic complete response (pCR) after NAC and have a better outcome than patients with residual disease. Purpose: The aim of this study is to identify clinical factors associated with the metastatic-free survival in TNBC patients who received NAC. Methods: We analyzed 326 cT1-3N1-3M0 patients with ductal infiltrating TNBC treated by NAC. The survival analysis was performed using a Cox proportional hazard model to determine clinical features associated with prognosis on the whole TNBC dataset. In addition, we built a recursive partitioning tree in order to identify additional clinical features associated with prognosis in specific subgroups of TNBC patients. Results: We identified the lymph node involvement after NAC as the only clinical feature significantly associated with a poor prognosis using a Cox multivariate model (HR = 3.89 [2.42-6.25], p<0.0001). Using our recursive partitioning tree, we were able to distinguish 5 subgroups of TNBC patients with different prognosis. For patients without lymph node involvement after NAC, obesity was significantly associated with a poor prognosis (HR = 2.64 [1.28-5.55]). As for patients with lymph node involvement after NAC, the pre-menopausal status in grade III tumors was associated with poor prognosis (HR = 9.68 [5.71-18.31]). Conclusion: This study demonstrates that axillary lymph node status after NAC is the major prognostic factor for triple-negative breast cancers. Moreover, we identified body mass index and menopausal status as two other promising prognostic factors in this breast cancer subgroup. Using these clinical factors, we were able to classify TNBC patients in 5 subgroups, for which pre-menopausal patients with grade III tumors and lymph node involvement after NAC have the worse prognosis.
    No preview · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Background: Trastuzumab was introduced a decade ago and has improved outcomes for HER2-positive breast cancer. We investigated the factors predictive of pathological complete response (pCR), prognostic factors for disease-free survival (DFS), and interactions between pCR and DFS after neoadjuvant treatment. Methods: We identified 287 patients with primary HER2-positive breast cancers given neoadjuvant chemotherapy (NAC) between 2002 and 2011. Univariate and multivariate analyses of clinical and pathological factors associated with pCR and DFS were performed. Results: pCR rates differed between patients receiving neoadjuvant trastuzumab treatment or not (47.7% versus 19.3%, P<0.0001). DFS also differed significantly between patients receiving adjuvant trastuzumab or not (hazard ratio=4.84, 95% CI (2.52; 9.31), P<0.001). We analysed 199 patients given neoadjuvant and adjuvant trastuzumab. Multivariate analysis identified older age and hormone receptor-negative tumours as independent predictors of pCR. T stage (hazard ratio=2.55, 95% CI (1.01; 6.48), P=0.05) and strict pCR (hazard ratio=9.15, 95% CI (1.22; 68.83), P=0.03) were independent predictors of DFS. The latter association was significant in the HR-negative subgroup (P=0.02) but not in the HR-positive subgroup (P=0.12). Conclusions: Major pCR and DFS gains in HER2-positive BC were observed since 'trastuzumab' era. Further improvements rely on the enrollment of accurately selected patients into clinical trials.British Journal of Cancer advance online publication 10 December 2015; doi:10.1038/bjc.2015.426 www.bjcancer.com.
    Full-text · Article · Dec 2015 · British Journal of Cancer
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    ABSTRACT: Nasal glomangiopericytoma is rare. The immunophenotype is heterogeneous, more frequently smooth-muscle-actin and CD34-positive. We report expression patterns for several vascular-related proteins such as CD99, CD146, Bcl2, and WT1 as well as for treatment-related proteins such as mTOR and EGFR in a nasal glomangiopericytoma. The patient (woman, 86 years) presented with a left nasal tumefaction. The resected specimen (1.5-cm) showed a glomangiopericytoma. Tumor cells expressed smooth-muscle-actin, CD31, CD34, and progesterone receptor. They also expressed the vascular-cell-related proteins Bcl2, CD99, CD146, and WT1, as well as mTOR and EGFR. Nasal glomangiopericytomas show immunohistochemical heterogeneity for vascular-related markers, suggesting a possible extensive pericytic differentiation. The expression of potential targets for drug treatments such as mTOR and EGFR may impact on the clinical follow-up of these tumors occurring at advanced ages, which may require complex surgery.
    Full-text · Article · Sep 2015
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    ABSTRACT: Secretory breast carcinoma (SBC) is a rare breast carcinoma with distinctive morphologic features and a recurrent specific chromosomal translocation t(12;15)(p13;q25), usually of low histologic grade and favorable prognosis. We describe the morphologic and genetic characteristics of 11 cases of SBC from 10 patients. Histologic and immunohistochemical analyses, fluorescence in situ hybridization using break-apart probes specific to ETV6 on 12p13, reverse transcription polymerase chain reaction with in-house probes specific to the ETV6-NTRK3 gene fusion, and DNA copy number variation by array comparative genomic hybridization analyses were performed on all cases. Seven cases were of low histologic grade, 3 were intermediate, and 1 had high-grade nuclear atypia, necrosis, and numerous mitoses. This patient had a fatal outcome. Five cases displayed low hormonal receptor expression, whereas the rest had basal-type immunoprofiles. All interpretable cases harbored an ETV6-NTRK3 gene fusion by reverse transcription polymerase chain reaction and/or an ETV6 rearrangement by fluorescence in situ hybridization, with duplication of the oncogenic derivative in 2 cases. Array comparative genomic hybridization analysis showed simplex genomic profiles. The 2 cases with ETV6-NTRK3 duplication included a gain of 12p starting from the ETV6 locus to the telomere, associated with a gain of the 15q from the centromere to NTRK3 in 1 case, and in the other a normal profile up to NTRK3 on 15q, and then a loss up to the telomere, suggesting loss of corresponding normal chromosome 15. These findings provide a novel insight into the morphologic and genetic spectrum of SBC, ranging from low-grade to high-grade histology, with occasional low hormonal receptor expression, simplex genomic profiles, and possible unfavorable course.
    No preview · Article · Aug 2015 · The American journal of surgical pathology
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    ABSTRACT: Because desmoid tumors (DT) exhibit an unpredictable clinical course, translational research is crucial to identify the predictive factors of progression in addition to the clinical parameters. The main issue is to detect patients who are at a higher risk of progression. The aim of this work was to identify molecular markers that can predict Progression-Free Survival (PFS). Gene-expression screening was conducted on 115 available independent untreated primary desmoid tumors using cDNA microarray. We established a prognostic gene expression signature composed of 36 genes. To test robustness, we randomly generated 1000 36-gene signatures and compared their outcome association to our define 36-genes molecular signature and we calculated Positive Predictive Value and Negative Predictive Value. Multivariate analysis showed that our molecular signature had a significant impact on PFS while no clinical factor had any prognostic value. Among the 1000 random signatures generated, 56.7% were significant and none was more significant than our 36-gene molecular signature. Positive and negative predictive value was high (75.58% and 81.82% respectively). Finally, the top two genes down-regulated in no-recurrence were FECH and STOML2 and the top gene up-regulated in no-recurrence was TRIP6. By analyzing expression profiles, we have identified a gene expression signature that is able to predict Progression-Free Survival. This tool may be useful for prospective clinical studies. Copyright © 2015, American Association for Cancer Research.
    Preview · Article · Apr 2015 · Clinical Cancer Research
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    ABSTRACT: Breast angiosarcomas are rare vascular malignancies that arise secondary to irradiation or de novo as primary tumours. The aim of this study is to know whether c-myc amplification can reliably discriminate these two entities. Forty-seven patients treated for breast angiosarcomas were studied. Thirty-two patients were diagnosed with postradiation angiosarcomas after breast cancer treatment and 15 patients with primary angiosarcomas. Interphase fluorescence in situ hybridization (FISH) was performed by hybridization of probes covering C-MYC (chromosome 8q24.21) and CEP8 on tissue sections. Amplification (5- to 20-fold) of the c-myc oncogene was found in all breast radiation-induced angiosarcomas (32 tumours) but in none of the 15 primary angiosarcomas except one (7%). This study reinforces that there are true pathogenetic differences between the two types of breast angiosarcomas which are morphologically indistinguishable. These data point the pathways preferentially involved in the pathogenesis of post radiation angiosarcomas of the breast and may provide the basis for an additional targeted therapy. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.
    No preview · Article · Apr 2015 · Cancer/Radiothérapie
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    ABSTRACT: In France, endometrial cancer is at the first rank of gynecological cancers for cancer incidence, before ovarian and cervical cancers. In fact, the number of incident cases has been estimated to 7275 for the year 2012; the number of death due to endometrial cancer to 2025. This cancer is hormone-dependent and endogenous (reproductive factors) or exogenous (oral combined contraceptives, hormone replacement therapy) causes of exposition to estrogens are the major environmental risk factors for both types of endometrial cancers: type I or well-differentiated endometrioid adenocarcinomas; and type II including all other histological types: papillary serous adenocarcinomas, clear cell adenocarcinomas and carcinosarcomas, also known as malignant mixed Mullerian tumor, MMMT. Obesity, diabetes mellitus and adjuvant treatment of breast cancer with tamoxifen are also associated with an increased risk of endometrial cancer. Genetic factors may also be implicated in the pathogenesis of endometrial cancer either as "minor genetic factors" (susceptibility factors), which remain largely unknown and are responsible for the increased observed risk in relatives of women affected with endometrial cancer; or as major genetic factors responsible for hereditary forms and namely for Lynch syndrome whose genetic transmission is of autosomic dominant type. The appropriate recognition of Lynch syndrome is of critical importance because affected patients and their relatives should benefit from specific care. The aims of this review is to describe major environmental and genetic risk factors for endometrial cancer with specific attention to most recent advances in this field and to describe recommendations for care of at-risk women. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
    Full-text · Article · Feb 2015 · Bulletin du cancer

  • No preview · Article · Dec 2014 · Radiotherapy and Oncology
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    ABSTRACT: BACKGROUND In the medical literature many analyses of outcomes of sarcoma patients were performed without regard to the problem of “competing risks.”METHODS We analyzed local relapse–free and metastasis-free survival in a population of 3255 adult patients with a primary soft-tissue sarcoma (STS) included in the French Sarcoma Group database. Cumulative incidence of local and metastatic relapse was estimated by accounting for death as a competing event.RESULTSOn multivariate analysis, age, tumor site, histological subtype, and grade were independent adverse prognostic factors for local relapse, whereas tumor depth and size had no influence. Histological subtype, tumor depth, tumor size, and grade were independent adverse prognostic factors for metastatic relapse. Despite a higher incidence of competing deaths in patients managed with adjuvant radiotherapy than in patients not receiving radiotherapy, adjuvant radiotherapy was associated with a significant benefit in terms of local relapse–free survival. Despite a similar cumulative incidence of competing deaths in patients with grade 2 and grade 3 disease, we found that the benefit of adjuvant chemotherapy was present only in patients with grade 3 and not in patients with grade 2 disease.CONCLUSIONS In the setting of competing risks, tumor biology reflected by histological grade is a crucial predictor of local relapse, whereas tumor depth and size have poor if any influence. Grade could also predict the benefit of adjuvant chemotherapy in patients with STS. Cancer 2014. © 2014 American Cancer Society.
    No preview · Article · Nov 2014 · Cancer
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    ABSTRACT: Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Oct 2014 · Annales de Pathologie
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    ABSTRACT: Background: To the authors' knowledge, the incidence of late recurrence (> 5 years after initial management) is unknown and no prognostic factors for late events have been characterized in patients with soft tissue sarcomas. Methods: Follow-up data from patients with localized soft tissue sarcoma who were included in the French Sarcoma Group database from January 1990 to June 2005 were reviewed. The outcomes of interest were the cumulative probabilities of late (> 5 years) local and metastatic disease recurrence with death as a competing event. Estimations and 95% confidence intervals (95% CIs) were computed with the cumulative incidence function. Results: A total of 719 patients who were alive and event free > 5 years after their initial diagnosis were included in the current study. Sixty-seven patients (9.3%) developed a late local recurrence and 42 patients (5.8%) developed a late metastatic recurrence, respectively. On multivariate analysis, internal trunk location (hazard ratio [HR], 3.9; 95% CI, 2.2-6.7 [P < .001]) and tumor size > 100 mm (HR, 2.1; 95% CI, 1.1-4 [P = .035]) were the 2 factors found to be independently associated with an increased risk of late local recurrence. Grade > 1 (graded according to the French Federation of Cancer Centers Sarcoma Group) (HR, 4.7; 95% CI 1.1-21 [P = .04]) was the sole factor found to be independently associated with an increased risk of late metastatic recurrence. Conclusions: Late recurrence of soft tissue sarcoma is relatively uncommon. However, the results of the current study emphasize the critical role of long-term follow-up to detect late local disease recurrence in patients with retroperitoneal or very large soft tissue sarcomas, and late metastatic recurrence in patients with high-grade disease. Conversely, the prolonged follow-up of patients with grade 1 disease is not needed.
    No preview · Article · Oct 2014 · Cancer
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    ABSTRACT: Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma.
    No preview · Article · Oct 2014 · Annales de Pathologie
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    ABSTRACT: While absent from normal epithelia, an actin bundling protein, fascin, become expressed in invasive carcinoma of different origins. It is highly enriched at the tumors’ invasive fronts suggesting that it could play a role in cancer invasion. Multiple studies have shown that fascin, through its role in formation of cellular protrusions such as filopodia and invadopodia, enhances cancer cell migration and invasion in vitro. However, the role of fascin in vivo remains unknown. We have generated a compound transgenic mouse model that allows expression of fascin in the intestinal epithelium in the Apc-mutated background. Conditional expression of fascin led to decrease in mice survival and increase in tumor burden compared to control animals. Induction of fascin expression in adult tumor-bearing animals accelerated tumor progression and led to formation of invasive adenocarcinoma. Altogether, our study shows that fascin can promote tumor progression in vivo, but also unravels an unexpected role of fascin in tumor initiation.
    Full-text · Article · Sep 2014 · European Journal of Cell Biology
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    ABSTRACT: Objective The aim of this study was to determine the frequency of primary sinonasal adult sarcoma, identify histological subtypes, and analyze prognostic factors.Study DesignRetrospective review.Method Forty-eight adult sinonasal sarcomas included in the French Sarcoma Group database (Conticabase) were reviewed.ResultsThe most frequent tumor types were alveolar rhabdomyosarcoma (33.3%), embryonal rhabdomyosarcoma (14,6%), unclassified sarcoma (14.6%), and leiomyosarcoma (12.5%). All round cell tumors were rhabdomyosarcomas. The 5-year overall survival (OS), metastasis-free survival (MFS), and local recurrence-free survival (LRFS) rates were 62.3%, 73%, and 88.8%, respectively. Histotype was a prognostic factor for OS, MFS, and LRFS, with the worst prognosis associated with rhabdomyosarcomas, regardless of the subtype. The tumor grade influenced the OS and MFS. Surgery was a predictive factor for a complete response.Conclusions These results suggest that sinonasal tract should be considered as an unfavorable site for rhabdomyosarcoma. Moreover, surgery should always be considered in treatment.Level of EvidenceN/A. Laryngoscope, 2014
    No preview · Article · Sep 2014 · The Laryngoscope
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    ABSTRACT: BACKGROUND Desmoplastic small round cell tumor (DSRCT) is a rare round cell sarcoma entity characterized by a specific t(11;22)(p13;q12) translocation, usually intra-abdominal localization and an aggressive clinical outcome. To date, only 35 DSRCT cases diagnosed by fine-needle aspiration have been described.METHODS This study reports the cytological diagnosis of DSRCT. Ten tumors from 8 patients were sampled for diagnosis and analyzed to search the characteristic translocation using fluorescence in situ hybridization or reverse transcription polymerase chain reaction methods.RESULTSSmears were always hypercellular and consisted of nonspecific round cell sarcoma. Nuclei were polymorphic round, kidney-, or heart-shaped. Nuclear molding was usually present. Paranuclear cytoplasmic densities were obvious and noted in 7 cases. Cytonuclear atypia, mitotic figures, numerous crushed nuclei, and apoptosis were frequently seen. Purple-stained stroma was present in 8 cases (ranging from few connective tissue fragments to large hyalinized deposits). Molecular studies based on cytological aspirates were performed in 8 patients. The presence of the fusion gene EWSR1-WT 1 transcript was identified in all, which confirmed the diagnosis of DSRCT.CONCLUSIONS Smears showing poorly differentiated round cells associated with cytoplasmic densities and connective stoma, in a specific clinical context, young adult age, intra-abdominal localization, suggestive immunocytochemical profile, and a unique cytogenetic abnormality are highly specific and allow an accurate diagnosis of DSRCT. Cancer (Cancer Cytopathol) 2014. © 2014 American Cancer Society.
    No preview · Article · May 2014 · Cancer Cytopathology
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    ABSTRACT: Rhabdomyosarcoma (RMS) is a soft tissue sarcoma categorized into two major subtypes: alveolar RMS (ARMS) and embryonal RMS (ERMS). Most ARMS express the PAX3-FOXO1 (P3F) fusion oncoprotein generated by the 2;13 chromosomal translocation. In the present study, the downstream target genes of P3F were identified by analyzing two independent sets of gene expression profiles: primary RMS tumors and RD ERMS cells transduced with inducible P3F constructs. We found 34 potential target genes (27 upregulated and 7 downregulated) that were significantly and differentially expressed between P3F-positive and P3F-negative categories, both in primary RMS tumors and in the inducible P3F cell culture system. Gene ontology analysis of microarray data of the inducible P3F cell culture system employed indicated apoptosis, cell death, development, and signal transduction as overrepresented significant functional categories found in both upregulated and downregulated genes. Therefore, among the 34 potential target genes, the expression of cell death‑related [Gremlin1, cysteine knot superfamily 1, BMP antagonist 1 (GREM1) and death-associated protein kinase 1 (DAPK1)] and development‑related [myogenic differentiation 1 (MYOD1) and hairy/enhancer-of-split related with YRPW motif 1 (HEY1)] genes were further investigated. The differential expression of GREM1, DAPK1, MYOD1 and HEY1 was confirmed in independent tumors and inducible cell culture systems. The expression of GREM1, DAPK1 and MYOD1 were significantly upregulated; HEY1 was significantly downregulated in independent P3F-positive ARMS tumors and transcriptionally active P3F cells, compared to those in ERMS tumors and transcriptionally inactive P3F cells. This study identified target genes of P3F and suggested that four downstream targets (GREM1, DAPK1, MYOD1 and HEY1) can contribute to the biological activities of P3F involved in growth suppression or cell death and myogenic differentiation.
    No preview · Article · Jun 2013 · Oncology Reports
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    ABSTRACT: Oncogenic rearrangements of the TFE3 transcription factor gene are found in two distinct human cancers. These include ASPSCR1-TFE3 in all cases of alveolar soft part sarcoma (ASPS) and ASPSCR1-TFE3, PRCC-TFE3, SFPQ-TFE3, and others in a subset of pediatric and adult RCCs. Here, we examined the functional properties of the ASPSCR1-TFE3 fusion oncoprotein, defined its target promoters on a genome-wide basis, and performed a high throughput RNA interference screen to identify which of its transcriptional targets contribute to cancer cell proliferation. We first confirmed that ASPSCR1-TFE3 has a predominantly nuclear localization and functions as a stronger transactivator than native TFE3. Genome-wide location analysis performed on the FU-UR-1 cell line which expresses endogenous ASPSCR1-TFE3 identified 2193 genes bound by ASPSCR1-TFE3. Integration of these data with expression profiles of ASPS tumor samples and inducible cell lines expressing ASPSCR1-TFE3 defined a subset of 332 genes as putative upregulated direct targets of ASPSCR1-TFE3, including MET (a previously known target gene), and 64 genes as down-regulated targets of ASPSCR1-TFE3. As validation of this approach to identify genuine ASPSCR1-TFE3 target genes, two up-regulated genes bound by ASPSCR1-TFE3, CYP17A1 and UPP1, were shown by multiple lines of evidence to be direct, endogenous targets of transactivation by ASPSCR1-TFE3. As the results indicated that ASPSCR1-TFE3 functions predominantly as a strong transcriptional activator, we hypothesized that a subset of its upregulated direct targets mediate its oncogenic properties. We therefore chose 130 of these upregulated direct target genes to study in high-throughput RNAi screens using FU-UR-1 cells. In addition to MET, we provide evidence that 11 other ASPSCR1-TFE3 target genes contribute to the growth of ASPSCR1-TFE3-positive cells. Our data suggest new therapeutic possibilities for cancers driven by TFE3 fusions. More generally, this work establishes a combined integrated genomics / functional genomics strategy to dissect the biology of oncogenic, chimeric transcription factors. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Full-text · Article · Apr 2013 · The Journal of Pathology
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    ABSTRACT: Purpose: Data about the prognostic factors of soft-tissue leiomyosarcomas and their correlation with molecular profile are limited. Experimental design: From 1990 to 2010, 586 adult patients with a primary soft-tissue leiomyosarcoma were included in the French Sarcoma Group (GSF) database after surgery of the primary tumor. Multivariate analyses were conducted by Cox regression model in a backward stepwise procedure. Genetic profiling was conducted for 73 cases. Results: Median age was 59 years (range, 21-98 years). The median follow-up of patients alive was 46 months. The 5-year metastasis-free survival (MFS) rate was 51% (95% location and grade > I were independent adverse prognostic factors for MFS). The 5-year overall survival (OS) rate was 63% [95% confidence interval (CI), 59-67]. On multivariate analysis, age ≥ 60 years old, tumor size > 5 cm, deep location, and grade > I were independent adverse prognostic factors for OS. Molecular profiling identified specific clusters with activation of different biologic pathways: retroperitoneal leiomyosarcomas are characterized by overexpression of genes involved in muscle differentiation and nonretroperitoneal leiomyosarcomas characterized by overexpression of genes mainly involved in extracellular matrix, wounding, and adhesion pathways. The CINSARC signature but not comparative genomic hybridization (CGH) profiling was predictive of outcome. Conclusion: Soft-tissue leiomyosarcomas represent a heterogeneous group of tumors with at least two categories, retroperitoneal and extremities leiomyosarcomas, having specific clinical outcome and molecular features. Future clinical trials should consider this heterogeneity for a better stratification of patients.
    No preview · Article · Jan 2013 · Clinical Cancer Research

  • No preview · Article · Dec 2012 · Cancer Research

Publication Stats

2k Citations
327.05 Total Impact Points

Institutions

  • 2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2007-2015
    • Institut Curie
      • Service de Radiothérapie
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • University of Washington Seattle
      • Department of Pathology
      Seattle, WA, United States
  • 2006-2013
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pathology
      New York, New York, United States
  • 2005
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, MD, United States