Papers by Isabelle Treilleux
Cancer Research, 2009
Immunohistochemical analysis of FOXP3 in primary breast tumors showed that a high number of tumor... more Immunohistochemical analysis of FOXP3 in primary breast tumors showed that a high number of tumor-infiltrating regulatory T cells (Ti-Treg) within lymphoid infiltrates surrounding the tumor was predictive of relapse and death, in contrast to those present within the tumor bed. Ex vivo analysis showed that these tumor-infiltrating FOXP3+ T cells are typical Treg based on their CD4+CD25highCD127lowFOXP3+ phenotype, their anergic state on in vitro stimulation, and their suppressive functions. These Ti-Treg could be selectively recruited through CCR4 as illustrated by (a) selective blood Treg CCR4 expression and migration to CCR4 ligands, (b) CCR4 down-regulation on Ti-Treg, and (c) correlation between Ti-Treg in lymphoid infiltrates and intratumoral CCL22 expression. Importantly, in contrast to other T cells, Ti-Treg are selectively activated locally and proliferate in situ, showing T-cell receptor engagement and suggesting specific recognition of tumor-associated antigens (TAA). Immun...
In breast cancer bone metastasis, tumor cells stimulate osteoclast-mediated bone resorption, and ... more In breast cancer bone metastasis, tumor cells stimulate osteoclast-mediated bone resorption, and bone-derived growth factors released from resorbed bone stimulate tumor growth. The AvB3 integrin is an adhesion receptor expressed by breast cancer cells and osteoclasts. It is implicated in tumor cell invasion and osteoclast-mediated bone resorption. Here, we hypothesized that the therapeutic targeting of tumor AvB3 integrin would prevent
Histopathology, 2015
FOXL2 mutation has been consistently identified in adult granulosa cell tumors (A-GCT). DICER1 mu... more FOXL2 mutation has been consistently identified in adult granulosa cell tumors (A-GCT). DICER1 mutations have been described predominantly in Sertoli-Leydig cell tumors (SLCT). The prognostic implication of these mutations remains uncertain as moderately sized studies have yielded variable outcomes. Our aim was to determine the implications of DICER1 and FOXL2 mutations in 156 ovarian SCST. FOXL2 mutation was detected in 94% of pathologically confirmed A-GCT (95/101), in 1/8 J-GCT and in 2/19 SLCT. DICER1 mutations in the RNase IIIb domain were found in 6 of 19 SLCT, 2 of 8 J-GCT and 1 of 12 Und-SCST. Comparison of SLCT with or without DICER1 mutation show that patient age at diagnosis was younger and ER expression more frequent in DICER1 mutated tumors. With a median of follow up of 22 months, 2 of 5 SLCT with mutated DICER1 relapse in contrast to 0 of 8 DICER1 non-mutated tumors. Our results suggest that in contrast to FOXL2 mutation in A-GCT, DICER1 mutation in SLCT might be useful more for prognosis than for diagnosis. But study of a larger cohort of patients is necessary to establish this. Identification of genetic alterations in SCST offers promising therapeutic options. This article is protected by copyright. All rights reserved.
PLOS ONE, 2015
Protein arginine methylation is a common post translational modification that regulates protein p... more Protein arginine methylation is a common post translational modification that regulates protein properties. This modification is carried out by a family of nine arginine methyltransferases (PRMTs). Arginine methylation has already been linked to tumourigenesis as overexpression of these enzymes was associated with various cancers, notably in breast cancers. Since the Jumonji Domain Containing 6 protein (JMJD6) possesses an arginine demethylase activity able to remove the methyl mark, we wanted to assess its potential role in breast tumourigenesis.
European Journal of Cancer Supplements, 2008
British journal of cancer, Jan 18, 2009
Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small inter... more Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription-PCR. We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic im...
Carcinogenesis, Jan 30, 2015
Granulosa cell tumor (GCT) is a rare and severe form of sex-cord stromal ovarian tumor that is ch... more Granulosa cell tumor (GCT) is a rare and severe form of sex-cord stromal ovarian tumor that is characterized by its long natural history and tendency to recur years after surgical ablation. Because there is no efficient curative treatment beyond surgery, ~20% of patients die of the consequences of their tumor. However, very little is known of the molecular etiology of this pathology. About 70% of GCT patients present with elevated circulating estradiol (E2). Because this hormone is known to increase tumor growth and progression in a number of cancers, we investigated the possible role of E2 in GCTs. Cell-based studies with human GCT metastases and primary tumor-derived cells, i.e. KGN and COV434 cells, respectively, aimed at evaluating E2 effect on cell growth, migration and invasion. Importantly, we found that E2 did not affect GCT cell growth, but that it significantly decreased the migration and matrix invasion of metastatic GCT cells. Noteworthy, our molecular studies revealed t...
British journal of cancer, Jan 19, 2003
Determination of the HER2/neu (HER2) status in breast carcinoma has become necessary for the sele... more Determination of the HER2/neu (HER2) status in breast carcinoma has become necessary for the selection of breast cancer patients for trastuzumab therapy. Amplification of the gene analysed by fluorescence in situ hybridisation (FISH) or overexpression of the protein determined by immunohistochemistry (IHC) are the two major methods to establish this status. A strong correlation has been previously demonstrated between these two methods. However, FISH is not always feasible in routine practice and weakly positive IHC tumours (2+) do not always correspond to a gene amplification. Our study was performed in order to evaluate the contribution of chromogenic in situ hybridisation (CISH), which enables detection of the gene copies through an immunoperoxidase reaction. CISH was performed in 79 breast carcinomas for which the HER2 status was previously determined by IHC and FISH. The results of IHC, FISH and CISH were compared for each tumour. CISH procedures were successful in 95% of our c...
Cancer research, 2001
Tubulin, the dimeric subunit of microtubules, is a major cell protein that is centrally involved ... more Tubulin, the dimeric subunit of microtubules, is a major cell protein that is centrally involved in cell division. Tubulin is subject to specific enzymatic posttranslational modifications including cyclic tyrosine removal and addition at the COOH terminus of the alpha-subunit. Tubulin is normally extensively tyrosinated in cycling cells. However, we have previously shown that detyrosinated tubulin accumulates in cancer cells during tumor progression in nude mice. Tubulin detyrosination, resulting from suppression of tubulin tyrosine ligase and the resulting unbalanced activity of tubulin-carboxypeptidase, apparently represents a strong selective advantage for cancer cells. We have now analyzed the occurrence and significance of tubulin detyrosination in human breast tumors. We studied a total of 134 breast cancer tumors from patients with or without known complications over a follow-up period of 31 +/- 10 months. The mean age of the patients at the time of diagnosis was 57 years. Fo...
Cancer research, 1998
The most important subgroup of breast cancer patients for which reliable prognostic factors are n... more The most important subgroup of breast cancer patients for which reliable prognostic factors are needed are women without axillary lymph node involvement. Although overall, these patients have a good prognosis, it is known that 20-30% will experience a recurrence of the disease. To determine the prognostic significance of P53 tumor suppressor gene mutation, specimens from 113 primary breast cancers were evaluated for the presence of P53 alterations, as detected by cDNA sequencing of the entire coding sequence of the gene. The median follow-up for patients was 105 months. P53 gene mutation was an independent prognostic marker of early relapse and death. Our results suggest that P53 gene mutations could be an important factor to identify node-negative patients who have a poor prognosis in the absence of adjuvant therapy. Prospective studies should be designed to determine which therapy should be performed in this subgroup of patients.
Clinical Breast Cancer, 2009
Breast cancer is the second most common cause of central nervous system (CNS) metastases, which a... more Breast cancer is the second most common cause of central nervous system (CNS) metastases, which affect 14%-20% of patients with breast cancer 1 and typically occur late in the course of the disease. The prognosis is poor, with a median overall-survival (OS) of 6 months, 2 and this figure has not changed over the past 25 years. Recent series have raised the possibility that, with more effective systemic treatment, CNS metastases might become increasingly prevalent.
Stem Cell Reports, 2015
Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At... more Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer.
Clinical Breast Cancer, 2002
Breast cancer is one of the most common cancers in women and, despite advances in both diagnosis ... more Breast cancer is one of the most common cancers in women and, despite advances in both diagnosis and treatment, it is still the first cause of cancer death in women. Numerous compounds and chemotherapy regimens have proven efficacious in patients with metastatic breast cancer (MBC), although none of them are curative. 1 Selecting the most appropriate and effective treatment according to the individual tumor biological profile is of utmost importance in improving the outcome in MBC patients. This approach would avoid toxicity to those patients defined as resistant to a given chemotherapy regimen and would largely decrease the cost-effectiveness ratio by selecting the patients sensitive to the same regimen.
Molecular Oncology, 2014
We aimed at highlighting the role of ZNF217, a Krüppel-like finger protein, in Estrogen Receptor-... more We aimed at highlighting the role of ZNF217, a Krüppel-like finger protein, in Estrogen Receptor-α (ERα)-positive (ER+) and luminal breast cancers. Here we report for the first time that ZNF217 and ERα proteins bind to each other in both breast cancer cells and breast tumour samples, via the ERα hinge domain and the ZNF217 C-terminal domain. ZNF217 enhances the recruitment of ERα to its estrogen response elements (ERE) and the ERα-dependent transcription of the GREB1 estrogen-regulated gene. The prognostic power of ZNF217 mRNA expression levels is most discriminatory in breast cancers classified with a "good prognosis", particularly the Luminal-A subclass. A new immunohistochemistry ZNF217 index, based on nuclear and cytoplasmic ZNF217 staining, also allowed the identification of intermediate/poor relapse-free survivors in the Luminal-A subgroup. ZNF217 confers tamoxifen resistance in ER+ breast cancer cells and is a predictor of relapse under endocrine therapy in patients with ER+ breast cancer. ZNF217 thus allows the re-stratification of patients with ER+ breast cancers considered as cancers with good prognosis where no other biomarkers are currently available and widely used. Here we propose a model in ER+ breast cancer where ZNF217-driven aggressiveness incorporates ZNF217 as a positive enhancer of ERα direct genomic activity and where ZNF217 possesses its highest discriminatory prognostic value.
European Journal of Cancer Supplements, 2007
World Journal of Surgery, 2000
The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for in... more The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for invasive breast cancer and the predictability of axillary node status. Between January 1996 and June 1997 a total of 73 patients underwent patent blue dye lymphatic mapping and sentinel node biopsy followed by standard (level I and II) axillary node dissection (one bilateral procedure). The sentinel node was identified in 82.4% (61/74) of the cases and was predictive of axillary status in 96.7% (59/61). The false-negative rate of the procedure was 8.0% (2/25). The sentinel node was involved in 37.7% (23/61) and was the only one invaded in 30.4% (7/23). The sensitivity of the procedure was 92% (CI95% 74-99%) and its specificity 100%. It is currently considered to be an attractive new procedure undergoing evaluation in prospective controlled trials. This study confirmed the reliability and reproducibility of intraoperative lymphatic mapping and sentinel node biopsy. This is the first step toward a new era of minimally invasive axillary surgery for breast cancer.
The American Journal of Surgery, 2008
BACKGROUND: Atypical ductal hyperplasia (ADH) is diagnosed in 4% to 10% of directional vacuum-ass... more BACKGROUND: Atypical ductal hyperplasia (ADH) is diagnosed in 4% to 10% of directional vacuum-assisted stereotactic biopsies (DVABs) performed for microcalcifications. Since the underestimation rate varies from 7% to 36%, surgical excision is still recommended, although some authors have tried to identify a subset of patients who can be spared surgery.
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Papers by Isabelle Treilleux