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Biomedical subjects

Maryse Fiche

Publications and source records attributed to Maryse Fiche.

12 recordsLinked to original sources
PubMed2006

Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism.

Wnt and Notch signaling have long been established as strongly oncogenic in the mouse mammary gland. Aberrant expression of several Wnts and other components of this pathway in human breast carcinomas has been reported, but evidence for a causative role in the human disease has been missing. Here we report that increased Wnt signaling, as achieved by ectopic expression of Wnt-1, triggers the DNA damage response (DDR) and an ensuing cascade of events resulting in tumorigenic conversion of primary human mammary epithelial cells. Wnt-1-transformed cells have high telomerase activity and compromised p53 and Rb function, grow as spheres in suspension, and in mice form tumors that closely resemble medullary carcinomas of the breast. Notch signaling is up-regulated through a mechanism involving increased expression of the Notch ligands Dll1, Dll3, and Dll4 and is required for expression of the tumorigenic phenotype. Increased Notch signaling in primary human mammary epithelial cells is sufficient to reproduce some aspects of Wnt-induced transformation. The relevance of these findings for human breast cancer is supported by the fact that expression of Wnt-1 and Wnt-4 and of established Wnt target genes, such as Axin-2 and Lef-1, as well as the Notch ligands, such as Dll3 and Dll4, is up-regulated in human breast carcinomas.

Animals↗
PubMed2005

Identification of molecular apocrine breast tumours by microarray analysis.

Previous microarray studies on breast cancer identified multiple tumour classes, of which the most prominent, named luminal and basal, differ in expression of the oestrogen receptor alpha gene (ER). We report here the identification of a group of breast tumours with increased androgen signalling and a 'molecular apocrine' gene expression profile. Tumour samples from 49 patients with large operable or locally advanced breast cancers were tested on Affymetrix U133A gene expression microarrays. Principal components analysis and hierarchical clustering split the tumours into three groups: basal, luminal and a group we call molecular apocrine. All of the molecular apocrine tumours have strong apocrine features on histological examination (P=0.0002). The molecular apocrine group is androgen receptor (AR) positive and contains all of the ER-negative tumours outside the basal group. Kolmogorov-Smirnov testing indicates that oestrogen signalling is most active in the luminal group, and androgen signalling is most active in the molecular apocrine group. ERBB2 amplification is commoner in the molecular apocrine than the other groups. Genes that best split the three groups were identified by Wilcoxon test. Correlation of the average expression profile of these genes in our data with the expression profile of individual tumours in four published breast cancer studies suggest that molecular apocrine tumours represent 8-14% of tumours in these studies. Our data show that it is possible with microarray data to divide mammary tumour cells into three groups based on steroid receptor activity: luminal (ER+ AR+), basal (ER- AR-) and molecular apocrine (ER- AR+).

Apocrine Glands↗
PubMed2005

Typical medullary breast carcinomas have a basal/myoepithelial phenotype.

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-line mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n=44) and non-TMBC grade III with no or low scores (n=160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n=17) and non-MBC grade III cases (n=140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R=2.29), MIB1 > 50 (R=3.80), ERBB2 negativity (R=2.24) and p53 positivity (RR=1.45).

Breast Neoplasms↗
PubMed2005

Prospective comparison of 3 gamma-probes for sentinel lymph node detection in 200 breast cancer patients.

UNLABELLED: Previous reports have shown that axillary sentinel lymph node (ASLN) radiodetection allows accurate axillary staging for patients with early breast cancer. Radioguided surgery implies the use of a gamma-probe to count the emitted radioactivity of marked ASLNs. Several gamma-probes are commercially available, each with its own properties. The clinical impact of the type of gamma-probe used for ASLN radiodetection remains to be evaluated. METHODS: Three commercially available gamma-probes were evaluated: a scintillator with a bismuth germanate crystal (probe A), a semiconductor with a cadmium telluride crystal (probe B), and a semiconductor with a cadmium zinc telluride crystal (probe C). Two hundred patients with early breast cancer were prospectively enrolled to undergo ASLN radiodetection and axillary lymphadenectomy. ASLN mapping consisted of injecting (99m)Tc-sulfur-colloid around the tumor. For each patient, sentinel lymph nodes were counted successively with the 3 probes and the sensitivity of each gamma-probe was determined from ASLN residual activity. The results of detection rates and false-negative rates for each probe were compared. RESULTS: Mean residual ASLN activity was 52 kBq (range, 0.07-189 kBq). Sensitivity was compared among the 3 probes and found to be best for probe A. The detection rate of probe A was significantly better than that of probe B (93% vs. 86%, P = 0.05) but not different from that of probe C (93% vs. 90%). No differences in false-negative rates were observed among the 3 probes. CONCLUSION: ASLN detection rate depends on the type of gamma-probe used. Because failure to detect the ASLN leads to complete axillary lymphadenectomy, involving local morbidity and other sequelae, the type of gamma-probe must be considered important for sentinel lymph node radiodetection.

Breast Neoplasms↗
PubMed2004

Validation of axillary sentinel lymph node detection in the staging of early lobular invasive breast carcinoma: a prospective study.

BACKGROUND: Previous reports have shown that regional lymph node involvement in patients with early-stage breast carcinoma can be evaluated by resection of axillary sentinel lymph nodes (ASLN). Axillary lymphadenectomy may be unnecessary in the absence of ASLN involvement. In the current study, the authors compared the results of ASLN resection in patients with lobular invasive carcinoma (LIC) with the results from patients with ductal invasive carcinoma (DIC) in terms of detection rates and false-negative rates. METHODS: For ASLN detection, technetium 99m sulfur-colloid and patent blue were injected around the tumor. Each patient underwent both ASLN resection and complete axillary lymphadenectomy. Detection rates and false-negative rates were evaluated in patients with LIC and in patients with DIC. RESULTS: Two hundred forty-three patients with invasive, early-stage breast carcinoma were enrolled in the study (208 patients with DIC and 35 patients with LIC). The median patient age, pathologic tumor size, hormone receptor status, and rates of involved lymph nodes were equivalent for both groups. ASLN detection and false-negative rates did not differ for patients with LIC and patients with DIC. CONCLUSIONS: The ASLN detection rate was not dependent on the pathologic type of invasive carcinoma. Pathologic examination of ASLN in patients with LIC and in patients with DIC predicted axillary lymph node status with the same predictive value in terms of lymph node metastasis. For patients with LIC, ASLN examination overestimated the rate of micrometastasis as diagnosed by immunohistochemical techniques. These results will require confirmation in larger studies.

Aged↗
PubMed2004

Acquired hemophilia as first manifestation of breast carcinoma in a man under long-term spironolactone therapy.

A 69-year-old man under long-term spironolactone therapy (16 years) was hospitalized with spontaneous hematoma on the trunk and extremities. Coagulation studies disclosed an acquired hemophilia that was successfully treated with human factor VIII for a few days and immunosuppressive agents for several months. Physical examination revealed bilateral gynecomastia and an upper left quadrant breast nodule. Complete staging was unremarkable. Complete left mastectomy was performed. Histopathology showed invasive ductal carcinoma, expressing positivity for estrogen and progesterone receptors. The acquired hemophilia was considered to be a paraneoplasic syndrome. The question of a linkage between long-term spironolactone therapy and breast carcinoma is discussed.

Aged↗
PubMed2003

[HER2 gene amplification assay: is CISH an alternative to FISH?].

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

Breast Neoplasms↗
PubMed2003

[Ductal carcinoma in situ: current anatomo-pathologic data].

Ductal carcinoma in situ (DCIS), accounting for 15-25% of all breast cancers, is frequently diagnosed by mammographic examination. This heterogeneous disease requires a rigorous local treatment based, in about two-third of cases, on conservative surgery and radiotherapy. DCIS are currently classified on the basis of nuclear grade. Most lesions, and especially high nuclear grade DCIS, are limited to one quadrant. Micropapillary DCIS are likely to be of larger size/extent and thus a conservative approach is often difficult. A careful pathological examination of an oriented excisional biopsy is a pre-requisite for optimal therapy.

Biopsy↗
PubMed2003

[Network for sentinel lymph node research in breast cancer].

AIMS: The goals of this paper were to determine the accuracy of the sentinel node in predicting axillary nodal status and to evaluate the feasibility of incorporating sentinel node biopsy into a general practice. METHODS: Between June 1999 and February 2003, 304 patients with clinically T0-T2[< 3 cm] M0 breast cancer underwent sentinel node biopsy. Both lymphoscintigraphy and blue dye were used to guide this biopsy. The procedure was followed by a complete axillary dissection in the first patients and when the sentinel node was positive. Sentinel nodes were evaluated using serial levels of hematoxylin eosin staining, and cytokeratin immunohistochemistry. RESULTS: The overall sentinel node detection rate was 99% (301 of 304 patients). The accuracy of the identification in operating room was 98% (296 of 301 patients). The sentinel node was involved in 75 patients (25%): metastases (38 patients), micrometastases (32 patients) and isolated tumor cells (5 patients). The false negative rate was 0% and the negative predictive value 100%. CONCLUSION: Our results support that the sentinel node biopsy is an accurate predictor of axillary nodal status in patients with early breast cancer and implementing a network greatly facilitates its' discovery.

Adult↗
PubMed2002

Elevated (> or = 10%) MIB-1 proliferative index correlates with poor outcome in gastric stromal tumor patients: a study of 35 cases.

Mitotic activity and tumor size are currently regarded as the most powerful prognostic indicators for patients with gastrointestinal stromal tumor (GIST). This retrospective study evaluated the prognostic accuracy of MIB-1 proliferative index (PI) in combination with these two indicators in 35 GIST patients. Within a high-risk group, determined initially by tumor size and mitotic count, overall survival was significantly shorter for patients whose tumors had PI > or = 10% MIB-1 positive cells. When tumor location (gastric versus small intestine) was taken into account, a combination of tumor size, mitotic count, and PI > or = 10% identified a subgroup of patients with significantly shorter survival for gastric (but not small intestinal) GIST. Based on our results, MIB-1 immunostaining, when used in combination with tumor size and mitotic count, appears to be a powerful tool for identifying patients, especially those with gastric tumors, at high risk of recurrence and early tumor-related death.

Adult↗
PubMed2002

Rapid failure of pig islet transplantation in non human primates.

We have previously demonstrated that adult pig islets of Langerhans are not destroyed in vitro by primate sera. Whether these islets can function when placed into the liver of non-human primates is not known. We now report on the outcome of pig islet xenotransplantation into five non diabetic primates (four baboons and one macacus fascicularis) receiving intraportally purified adult pig islets. The average number of islet-equivalent per graft was 110,000 (60-180,000). All animals received associations of ATG, cyclosporine or LF 195 (a deoxyspergualin analog), mycophenolate mofetil and corticosteroids. A specific porcine C-peptide (C-pep) RIA test was used to monitor insulin secretion. Two hours after grafting, porcine C-peptide was positive (from 0.37 to 4.25 ng/ml) in all monkeys except one. Primate C-pep was normal in all cases. Only two monkeys had detectable levels of porcine C-pep on day 1 or 2 with undetectable levels thereafter, even after glucagon challenge between days 6 and 10. Several normal islets with moderate inflammatory infiltration were observed in one animal liver on day 2 (the time of necropsy) as well as islets with IgM and complement deposition. Among animals sacrificed on days 14, 16 and 38, some residual islet cells could be identified only in livers collected on day 14. Partial glycaemic control was achieved in some rats receiving islets from the same preparations. In conclusion, adult pig islets are not able to maintain insulin secretion for more than 24 h when injected intraportally into non diabetic immunosuppressed monkeys. suggesting immediate islet xenograft destruction.

Animals↗