Cécile Le Page

Cécile Le Page
McGill University Health Centre

PhD

About

126
Publications
11,977
Reads
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2,918
Citations
Citations since 2016
59 Research Items
1628 Citations
20162017201820192020202120220100200300
20162017201820192020202120220100200300
20162017201820192020202120220100200300
20162017201820192020202120220100200300
Introduction
Interest in molecular biomarkers in gynecologic cancers
Additional affiliations
December 2000 - August 2002
Geneka Inc.
Position
  • Researcher
Education
January 1994 - July 1998
Institut Curie
Field of study

Publications

Publications (126)
Article
Full-text available
This study aims to identify reliable prognosis markers to predict patient outcome at surgery in high-grade serous epithelial ovarian cancer by a real-time quantitative PCR (RT-q-PCR)-based test. Seventeen tissue samples from serous epithelial ovarian cancer patients were screened by DNA microarray to identify genes differentially expressed between...
Article
Full-text available
At least one third of all cases of epithelial ovarian cancer are associated with the production of ascites, although its effect on tumor cell microenvironment remains poorly understood. This study addresses the effect of the heterologous acellular fraction of ovarian cancer-derived ascites on a cell line (OV-90) derived from the chemotherapy-naïve...
Article
Full-text available
To further evaluate the association between the cytoplasmic or nuclear localization of ErbB3 with biochemical recurrence (BCR) in patients with prostate cancer and positive surgical margins, as there is a greater risk of BCR for such patients after radical prostatectomy (RP). We recently noted that ErbB3, which is normally associated with the plasm...
Article
Several reports suggest that androgen signalling interferes with canonical RelA-p50 activity in androgen-sensitive cells. Whether this also occurs with non-canonical NF-kappaB subunits has not been studied. Here we report that androgenic stimulation of LNCaP cells with the androgen analogue R1881 appears to positively regulate the non-canonical NF-...
Article
Full-text available
We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-...
Article
Cardiovascular diseases are leading causes of mortality and morbidity in adults worldwide. Multiple studies suggest that there are clinically relevant sex differences in cardiovascular disease. Women and men differ substantially in terms of prevalence, presentation, management, and outcomes of cardiovascular disease. To date, however, little is kno...
Article
Full-text available
Very recently, emerging evidence demonstrated that laterality might be an independent prognostic factor in patients with advanced ovarian cancer (OC). Based on preliminary provocative observations, our study aimed to investigate the prognostic impact of sidedness in a large cohort of women with OC. Survival was estimated based on Kaplan-Meier metho...
Article
Full-text available
Aims We aimed to characterize a large cohort of non-invasive, HPV and p53-independent verruciform lesions, such as “vulvar acanthosis with altered differentiation” (VAAD), “differentiated exophytic vulvar intraepithelial lesion” (DEVIL) and “verruciform lichen simplex chronicus” (vLSC). Methods and Results We retrospectively identified from Januar...
Article
Uterine sarcomas represent a clinical challenge because of their difficult diagnosis and the poor prognosis of certain subtypes. The aim of this study was to evaluate the expression of the special AT-rich sequence-binding protein 2 (SATB2) in endometrial stromal sarcoma (ESS) and other types of uterine sarcoma by immunohistochemistry. We studied th...
Article
Epithelial ovarian cancer (OC) is a heterogeneous disease and continues to be mostly diagnosed in advanced stages. The high lethality, the high rate of platinum-resistance, and the poor survival outcomes are the principal factors for categorizing OC among the most aggressive gynecological cancers. Only recently, a substantial progress has been made...
Article
Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion, thus regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so f...
Article
Full-text available
Low-grade serous ovarian carcinoma (LGSOC) is associated with a poor response to existing chemotherapy, highlighting the need to perform comprehensive genomic analysis and identify new therapeutic vulnerabilities. The data presented here represents the largest genetic study of LGSOC to date (n = 71), analysing 127 candidate genes derived from whole...
Article
BRCA1 and BRCA2 are multi-functional proteins and key factors for maintaining genomic stability through their roles in DNA double strand break repair by homologous recombination, rescuing stalled or damaged DNA replication forks, and regulation of cell cycle DNA damage checkpoints. Impairment of any of these critical roles results in genomic instab...
Article
TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mu...
Experiment Findings
A study cohort of more than 500 HGSOC patients treated with platinum-based chemotherapy and who underwent germline testing for BRCA1 was identified in the Canadian biobanks participating in the COEUR program. Chemoresistance response, treatment-free interval, progression-free survival and 5-years survival were analyzed. BRCA1 expression was evaluat...
Article
Full-text available
Objective: Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guide...
Article
Background: Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC). Methods: We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 E...
Article
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Although initial response rates to standard platinum-based treatment are at 70-80%, long-term response in advanced EOC disease is rarely achieved with the development of chemoresistance and recurrence, contributing to overall survival rates below 45%. Additional challenges s...
Article
Full-text available
Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across...
Article
Full-text available
The aim of this study was to describe the expression of special AT‐rich sequence‐binding protein 2 (SATB2) in ovarian endometrioid carcinoma (EC). SATB2 is a nuclear matrix‐associated transcription factor that is associated with abnormal expression in certain cancers but has not been reported for ovarian carcinoma. SATB2 mRNA and protein expression...
Article
The association between progesterone receptor (PR) expression and improved outcome of ovarian cancer patients has been reported with conflicting results (1). To clarify the prognostic role of PR expression patients, Luo et al. (1) performed a meta‐analysis of 28 published studies. The authors found that PR expression detected by immunohistochemistr...
Research
Study of progesterone receptor (PR) in the COEUR cohort clarifies the prognostic value of PR in a North American population.
Poster
Full-text available
Background: The Canadian Ovarian Experimental Unified Resource (COEUR) is a Canadian repository of epithelial ovarian cancer which provides researchers with biological material and associated clinical data to conduct biomarker validation studies. Here we describe the presence and prognostic value of germline BRCA mutations in the COEUR cohort . M...
Article
Full-text available
Background: Ovarian carcinoma is the most lethal gynecological malignancy due to early dissemination and acquired resistance to platinum-based chemotherapy. Reliable markers that are independent and complementary to clinical parameters are needed to improve the management of patients with this disease. The Canadian Ovarian Experimental Unified Res...
Article
Full-text available
Anoikis acts as a critical barrier to metastasis by inducing cell death upon cancer cell detachment from the extracellular matrix (ECM), thereby preventing tumor cell dissemination to secondary sites. The induction of anoikis requires the lysosomal-mediated downregulation of epidermal growth factor receptors (EGFRs) leading to termination of pro-su...
Data
Figure S1. High STAT1 expression associates with increased progression free survival and response to chemotherapy in HGSC Kaplan Meier estimates showing significant association between high STAT1 expression and increased progression free survival (p = 0.004) (S1A) and response to chemotherapy (p = 0.002) (S1B) in the CHUM validation cohort. STAT1...
Data
Figure S2. Intratumoural CD8+ T cells associate with overall survival in optimally debulked patients in CHUM cohort Kaplan Meier analysis was performed using intratumoral CD8+ T cell density (using average of two cores) dichotomized using the thresholds ≤ 5 vs >5 as established for ovarian cancer. Analysis was performed on optimally debulked cases...
Data
Figure S3. Intratumoural CD8+ T cells do not associate with progression free survival and response to chemotherapy in HGSC TFRI‐ COEUR cohort Kaplan Meier analysis was performed using intratumoral CD8+ T cell density (using average of two cores) dichotomized with the threshold of ≤ 5 vs >5 as established for ovarian cancer. Tumour samples were der...
Data
Figure S6. STAT1 expression correlates with MX1, IRF1 and IFITM1 expression in chemosensitive and resistant HGSCs Spearman correlation was performed between STAT1 and IRF1, MX1 and IFITM1 gene expression evaluated by NanoString analysis, within the sensitive and resistant tumours. Significant positive correlation was noted between the expression o...
Data
Table S4. Association between STAT1 expression and clinicopathological parameters Spearman correlation analysis was performed to determine the correlation between STAT1 expression as a continuous variable with age, grade, stage and debulking status
Data
Figure S7. STAT1 gene expression evaluated by NanoString assay correlates significantly with STAT1 protein expression evaluated by IHC Spearman correlation analysis showing significant positive correlation between STAT1 expression evaluated at mRNA and protein levels by NanoString and IHC, respectively (r=0.495, p < 10‐7)
Data
Table S3. Custom gene codeset used for NanoString gene expression analysis Custom gene panel designed for NanoString platform based gene expression analysis of total RNA derived from fresh frozen primary HGSC tumours. The gene panel primarily consists of STAT1 target genes in addition to a subset of immune cell phenotypic marker genes
Data
Table S5. Univariate and multivariate analysis of CD8 in the TFRI‐HGSC cohort Univariate and multivariate analysis of CD8 association with progression free survival (5A) and response to chemotherapy (5B) was performed in TFRI‐COEUR cohort (n=550)
Data
Figure S4. Differential expression of plasma cytokines in chemosensitive and resistant HGSC patients Multiplexed cytokine analysis of chemosensitive and resistant HGSC pre‐treatment plasma with age matched controls. Multiplexed cytokine analysis was performed on pre‐treatment plasma from HGSC patients classified as sensitive or resistant along wit...
Data
Table S1. Clinicopathological characteristics of CHUM (n = 184) and Phase TFRI‐COEUR (n = 550) high‐grade serous ovarian cancer cohorts Clinical and pathological characteristics of two independent cohorts of HGSC used for STAT1 and CD8 evaluation by immunohistochemistry
Data
Table S2. Univariate and multivariate analysis of STAT1 expression in TFRI‐COEUR HGSC cohort Univariate and multivariate analysis of STAT1 expression with progression free survival and response to chemotherapy was performed in TFRI‐COEUR cohort (n=550)
Data
Figure S5. STAT1 target chemokine genes correlate with CD8A expression in chemosensitive and resistant HGSCs Spearman correlation was performed between STAT1, CD8A, CXCL9, CXCL10 and CXCL11 gene expression within the sensitive and resistant tumours. Significant positive correlation was noted between STAT1 and CXCL10/CXCL11, CXCL10/CXCL11 and CD8A...
Article
Full-text available
High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predicti...
Article
Chemotherapy resistance is a major hurdle in high-grade serous epithelial ovarian cancer (HGSC) management. We previously reported differential expression of interferon inducible genes in pre-treatment tumours from chemoresistant and sensitive HGSC tumors. STAT1 expression was evaluated as a prognostic and predictive biomarker via immunohistochemis...
Article
Full-text available
TP53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low-grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has no...
Article
Full-text available
There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers...
Article
Full-text available
The Canadian Immunohistochemistry Quality Control provides proficiency testing for immunohistochemistry in Canadian laboratories. Canadian Immunohistochemistry Quality Control Run 42 assessed WT1, Napsin A, and p53; commonly used markers for histotyping ovarian carcinomas. A 42-core tissue microarray, which included the 5 major histotypes of ovaria...
Article
Full-text available
The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. While preclinical studies suggest that CD73 can be targeted for cancer treatment, the clinical impact of CD73 in ovarian cancer remains unclear. In this study, we investigated the prognostic value of CD73 in high-grade serous (HGS) ovaria...
Article
Full-text available
Background: While the classical NF-κB/p65 pathway is known to be involved in prostate cancer progression and is associated with poor patient outcome, the role of the NF-κB /RelB alternative protein is not well defined. Here we analyzed the activation of both NF-κB pathways in prostate cancer tissues and correlate this activation with clinical featu...
Article
Full-text available
ABSTRACT The taxanes are used alone or in combination with anthracyclines or platinum drugs to treat breast and ovarian cancer, respectively. Taxanes target microtubules in cancer cells and modifiers of taxane sensitivity have been identified in vitro, including drug efflux and mitotic checkpoint proteins. Human epidermal growth factor receptor 2 (...