Estrogen-Receptor, Progesterone-Receptor and HER2 Status Determination in Invasive Breast Cancer. Concordance between Immuno-Histochemistry and MapQuant™ Microarray Based Assay.

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 ¼ 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.

[Early prenatal interview knowledge in post-partum women: Cross-sectional study in 2011 in Lille (France)]. / Connaissance de l'entretien prénatal précoce chez les femmes venant d'accoucher : étude transversale en 2011 dans la métropole lilloise (France).

OBJECTIVES: Early prenatal interview (EPI) is one of the flagship measures of the 2005-2007 perinatal strategy. It allows mothers to have a 45-minute interview, distinct from a medical consultation, promoting the expression of their expectations and medical, psychological or social difficulties. It should be routinely offered to all mothers in early pregnancy. The main objective of our study was to determine the proportion of women who had knowledge of Early prenatal interview and to profile women who knew it. Secondary objectives were to describe the EPI achievement rate and its terms of implementation. MATERIALS AND METHODS: All women who gave birth between 16 and 20 January 2011 in one of the ten maternity hospitals of the Lille metropolis were interviewed during their stay in maternity. A mixed model logistic regression was made to draw the profile of women with knowledge of Early prenatal interview. RESULTS: Of 311 women who gave birth during the study period, 270 were included in the survey. 148 patients (54.8 %) knew Early prenatal interview and 79 (29.3 %) had it. Women who had a high level of education were significantly more aware of this interview than those with low level of study. Other factors studied were not significantly related to knowledge of the EPI. CONCLUSION: While the EPI should be routinely offered to all pregnant women, only half of the patients who give birth had heard about it during their pregnancy. Women of low educational level should be more targeted by professional performing this interview.

THE UNKNOWN SHADOWS OF TREHALASE.

Each year brings new facts concerning multiple roles of sugar pathways in plant metabolism. One of them--the trehalose pathway--has been shown to play a role in stress signalling. The last enzyme of this pathway--trehalase--has been proven to be strongly expressed in guard cells. Modifications of its abundance cause changes in stomatal closure and response to abscisic acid. Our phenotypical studies of different mutants of Arabidopsis thaliana and Musa have enabled us to propose a new function of trehalase. It might play a role in the feedback of sucrose as a closing signal for stomata in reaction to an efficient photosynthesis. To characterize the phenotype we measured: the dynamic cumulative water loss, the dynamic leaf surface temperature, and the stomatal conductance. Based on the obtained results we have determined the time points for a proteomics study. The exact role of trehalase and related proteins in the proposed mechanism will be defined with multiple analysis including mass spectrophotometry and enzymatic activities. The samples will be collected from a wide type of plants including model organism (Arabidopsis--wild type, trehalase mutant plants) and crops (banana). The final results will shed light on the complete role of trehalase and the feedback pathway.

Identification of the major regenerative III protein (RegIII) in the porcine intestinal mucosa as RegIIIγ, not RegIIIα.

During the last years, an antimicrobial protein from the RegIII family has been consistently identified as one of the main up-regulated mRNA transcripts in the pig small intestinal mucosa during different infections such as enterotoxigenic Escherichia coli (ETEC). This transcript has been mainly referred to in the literature as pancreatitis-associated protein (PAP/RegIIIα). However, the identity of this transcript has not been confirmed, and no evidence of its expression at the protein level is available in the literature, because the absence of a specific antibody. In this study, we first unequivocally identified the PAP/RegIII family protein mainly expressed in ETEC infected pig intestine as RegIIIγ by 2D-DIGE and MALDI-TOF/TOF. This shows that the pig differs from species like human and mice in that RegIIIγ (and not RegIIIα) might be the major RegIII isotype during intestinal infection. Immunoblotting analysis with a specifically generated polyclonal rabbit antibody revealed that pig RegIIIγ is expressed throughout the intestinal tract, but most abundantly in the ileum. Although a higher abundance of mRNA was paralleled by higher protein abundance, a lack of linear relationship was found between RegIIIγ mRNA and protein abundances in the jejunal mucosa, the latter most pronounced in the case of natural infection. This may be related to the secretory nature of RegIIIγ. This would mean that the antimicrobial protein RegIIIγ is a good candidate as a non-invasive faecal intestinal health biomarker in swine.

[Birth of a child with Down syndrome: parental choice or failure of screening policy?]. / Naissance d'un enfant porteur de trisomie 21: choix parental ou défaut de la politique de dépistage ?

OBJECTIVES: Birth of a child with Down syndrome (DS) can follow parental choice or failure of screening. The objective of this work is to describe the circumstances of births of children with DS in a French perinatal health network. METHODS: Retrospective multicentric study, with prospective trial registration of all children born alive with DS, between 2010 and 2013. RESULTS: Sixty-three children were born with DS. Complete screening was performed by 61 % of patients, incomplete screening by 29 % of patients and no screening test by 10 %. Among these births, 50 % occurred following parental choice, 40 % following failure of screening and for 10 %, parental choice concerning screening was unknown. False negative had often calculating risk close to 1/1000. CONCLUSION: In this study, the birth of a child with DS occurred following parental choice in half of cases. It's necessary, to optimize the follow-up, to document in medical records the medical information and parental choice concerning DS screening and data of screening when this was done.

Evaluation of transverse maxillary expansion after a segmental posterior subapical maxillary osteotomy in cleft lip and palate patients with severe collapse of the lateral maxillary segments.

Objective : The purpose of this longitudinal retrospective study was to evaluate transverse maxillary expansion after a Schuchardt or segmental posterior subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate (CLP). A second aim was to compare these data with data for adult patients without CLP who were receiving a surgical assisted rapid palatal expansion (SARPE). Method : The study group comprised 19 patients with CLP and a severe transversally collapsed maxilla who were treated with SPSMO followed by hyrax expansion at the University Hospitals Leuven. Dental casts of the 19 patients were analyzed before treatment, at maximum expansion, during orthodontic treatment, at the completion of orthodontic treatment. and 2 years after orthodontic treatment and were measured at the canine, premolar, and molar levels. Adult patients without CLP who were enrolled in a prospective study served as the control group. Results : Maxillary expansion within the study group was significantly greater (P < .05) at all measured levels compared with the maxillary arch before treatment. No significant relapse was measured in the study group 2 years after orthodontic treatment. When comparing the study and control groups, the only statistical difference was that canine expansion was significantly greater in the study group. Conclusion : SPSMO followed by maxillary expansion and orthodontic treatment is an appropriate treatment option to correct a severe transversally collapsed maxilla in patients with CLP. The overall treatment effect of SPSMO expansion is comparable with the effects of SARPE, although canine expansion was greater in the SPSMO group.

Evaluation of Transverse Maxillary Expansion After a Segmental Posterior Subapical Maxillary Osteotomy in Cleft Lip and Palate Patients With Severe Collapse of the Lateral Maxillary Segments.

Objective : The purpose of this longitudinal retrospective study was to evaluate transverse maxillary expansion after a Schuchardt or segmental posterior subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate (CLP). A second aim was to compare these data with data for adult patients without CLP who were receiving a surgical assisted rapid palatal expansion (SARPE). Method : The study group comprised 19 patients with CLP and a severe transversally collapsed maxilla who were treated with SPSMO followed by hyrax expansion at the University Hospitals Leuven. Dental casts of the 19 patients were analyzed before treatment, at maximum expansion, during orthodontic treatment, at the completion of orthodontic treatment. and 2 years after orthodontic treatment and were measured at the canine, premolar, and molar levels. Adult patients without CLP who were enrolled in a prospective study served as the control group. Results : Maxillary expansion within the study group was significantly greater (P < .05) at all measured levels compared with the maxillary arch before treatment. No significant relapse was measured in the study group 2 years after orthodontic treatment. When comparing the study and control groups, the only statistical difference was that canine expansion was significantly greater in the study group. Conclusion : SPSMO followed by maxillary expansion and orthodontic treatment is an appropriate treatment option to correct a severe transversally collapsed maxilla in patients with CLP. The overall treatment effect of SPSMO expansion is comparable with the effects of SARPE, although canine expansion was greater in the SPSMO group.

Cranio-maxillofacial, orthodontic and dental treatment in three patients with Apert syndrome.

BACKGROUND: Apert syndrome is a severe developmental malformation, clinically characterised by craniosynostosis, midface hypoplasia, a cone-shaped calvarium, ocular manifestations, typical dental findings and syndactyly of the hands and feet. Early craniosynostosis of the coronal suture, the cranial base and agenesis of the sagittal suture are prodromal characteristics for the typical craniofacial appearance in patients with Apert syndrome. CASE REPORTS: The aim of this report was to describe the maxillofacial and orthodontic management of three patients with Apert syndrome who attended the Craniofacial, Maxillofacial and Orthodontic clinics of the University Hospitals of the KU Leuven (Belgium). The typical clinical features, the general orthognathic treatment approach as well as individual approaches of three patients with Apert syndrome are being highlighted. FOLLOW-UP: The three patients with Apert syndrome have been followed up very closely by all involved specialised departments as well as by multidisciplinary teams from birth. CONCLUSION: This report demonstrated that a combined orthodontic and orthognathic surgical treatment plan could significantly improve the occlusal function as well as the facial and occlusal aesthetics in patients with Apert syndrome.

Neuropsychiatric systemic lupus erythematosus: association with global disease activity.

OBJECTIVE: To determine whether patients with neuropsychiatric (NP) events attributed to systemic lupus erythematosus (SLE) have more global disease activity than patients with NP events not attributed to SLE. METHODS: Patients were recruited from an academic lupus clinic. Global disease activity was measured with the SLE Disease Activity Index 2000 (SLEDAI-2K) and organ damage with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI). NP disease was defined using the ACR case definitions and decision rules for attribution of NP events to SLE and non-SLE causes. RESULTS: There were 68 patients (age (mean ± SD) 40.8 ± 15.2 years, 85% female, 94% Caucasians) with 126 NP events. SLEDAI-2K scores in patients with NP events attributed to SLE were higher than in patients with NP events attributed to non-SLE causes even when NP variables were removed from the SLEDAI-2K (mean ± SD: SLE NP = 7.36 ± 5.42 vs non-SLE NP = 5.53 ± 4.57, P = 0.042). Patients with CNS and diffuse NP events, rather that PNS and focal events, accounted for the group differences in SLEDAI-2K scores. There were no significant differences in total SDI scores comparing NP events due to SLE vs. non-SLE causes (mean ± SD: 2.1 ± 1.8 vs. 1.7 ± 1.7; p = 0.28) even when NP variables were omitted. CONCLUSIONS: Increased global SLE disease activity is associated with concurrent NP events attributed to SLE, particularly for diffuse NP and CNS NP events. The findings have diagnostic and therapeutic implications for SLE patients with NP events and inform pathogenetic mechanisms underlying NPSLE.

Enamel defects on the maxillary premolars in patients with cleft lip and/or palate: a retrospective case-control study.

AIM: The purpose of this study was to investigate the presence of developmental defects of enamel on maxillary premolars in patients with cleft lip and/or palate. In addition, the relationship with the surgical technique of soft palate closure was studied. Such a relationship could be suspected since formation of enamel occurs around the same time period as soft palate closure. MATERIALS AND METHODS: The study consisted of three groups. Patients from the first group (n = 123) were recruited from the Cleft Lip and Palate Team of the University Hospitals Leuven (CLPT-UHL). The second group (n = 81) consisted of patients consulting the Cleft Lip and Palate Team of the Radboud University Medical Centre Nijmegen (CLPT-UMCN). Healthy non-cleft lip and/or palate patients (n = 100) recruited from a private orthodontic practice were enrolled in group 3. All maxillary premolars were examined. RESULTS: Out of the total sample, 43 patients showed developmental defects on one or more premolars. All defects occurred in patients of group 1 who received surgical closure by the CLPT-UHL. None of the patients from group 2 and 3 showed defects. CONCLUSIONS: It can be suggested that the surgical technique, used by the CLPT-UHL for soft palate closure, causes these defects. It is postulated that the technique used by the CLPT-UHL leads to interference with the blood supply of the developing premolar at a critical stage of tooth enamel development. More research is needed to confirm these findings.

Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a recently delineated, autosomal recessive condition caused by rare mutations in the N-acylsphingosine amidohydrolase 1 (acid ceramidase) ASAH1 gene. It is characterized by motor neuron disease followed by progressive myoclonic seizures and eventual death due to respiratory insufficiency. Here we report an adolescent female who presented with atonic and absence seizures and myoclonic jerks and was later diagnosed as having myoclonic-absence seizures. An extensive genetic and metabolic work-up was unable to arrive at a molecular diagnosis. Whole exome sequencing (WES) identified two rare, deleterious mutations in the ASAH1 gene: c.850G>T;p.Gly284X and c.456A>C;p.Lys152Asn. These mutations were confirmed by Sanger sequencing in the patient and her parents. Functional studies in cultured fibroblasts showed that acid ceramidase was reduced in both overall amount and enzymatic activity. Ceramide level was doubled in the patient's fibroblasts as compared to control cells. The results of the WES and the functional studies prompted an electromyography (EMG) study that showed evidence of motor neuron disease despite only mild proximal muscle weakness. These findings expand the phenotypic spectrum of SMA-PME caused by novel mutations in ASAH1 and highlight the clinical utility of WES for rare, intractable forms of epilepsy.

[Influence of atmospheric pressure and its variations on premature rupture of membranes]. / Influence de la pression atmosphérique et de ses variations sur la rupture prématurée des membranes.

INTRODUCTION: In popular belief, a higher rate of premature rupture of membranes (PROM) might be associated with atmospheric pressure (AP) variations. Results of past studies are contradictory. We aimed to assess whether or not AP values influence the rate of PROM. MATERIAL AND METHODS: We performed a retrospective longitudinal study of women admitted for PROM from January 1st, 2009 to December 3rd, 2009. AP values for 2009 were obtained at the local meteorological station. RESULTS: AP values (average, minimum and maximum) and its variations did not influence the rate of PROM for 341 patients included in the study, as well as in the group of 187 patients with a negative result of vaginal swab or amniotic fluid sample. After exclusion of premature PROM, mean AP variation the days before PROM was higher than AP variations of the days without PROM (6.3hPa IC95% [5.65-7.00] vs. 5.2 IC95% [4.70-5.79], P=0.029). No higher rate of occurrence of PROM was noticed during the days with low AP (AP less than average AP of the year equal to 1009hPa or AP less than normal AP equal to 1013.2hPa) or during the days with a high variability (maximal AP-minimal AP greater than 5hPa). CONCLUSION: Our data did not support the hypothesis that AP influence the rate PROM.

The effect of inactivated Lactobacillus LB fermented culture medium on symptom severity: observational investigation in 297 patients with diarrhea-predominant irritable bowel syndrome.

INTRODUCTION: Little is known about the intensity of symptoms of diarrhea-predominant IBS (IBS-D) or the consequences of the disease on patients' health-related quality of life (HRQOL). This observational investigation assessed the symptoms (abdominal pain, bloating, number of stools per day, and stool consistency), impact on HRQOL, and consequence on anal continence in 297 patients with IBS-D before and after 1 month of probiotic treatment with Lacteol (inactivated Lactobacillus LB plus fermented culture medium). METHODS: Functional assessment using a standardized visual analogue scale in order to quantify abdominal pain, bloating, and quality of life before and after 1 month of treatment with 2 capsules/day of Lacteol. The number of symptomatic days per week, number of stools, consistency of stools, secondary fecal incontinence rate, and potential trigger effect of food were quantified. A χ2 test was used to compare qualitative data and the variance of quantitative criteria was analyzed. RESULTS: The pain score decreased from 4.46±0.15 on a scale of 0-10 before treatment to 2.8±0.14 after treatment (p<0.0001). Bloating decreased from 4.49±0.18 to 2.5±0.15 on a scale of 0-10 (p<0.0001). The HRQOL score, which is inversely correlated with quality of life, decreased from 5.99±0.14 to 3.92±0.16 (p<0.0001). In this cohort study, the fecal incontinence rate secondary to diarrhea was clearly higher than that of the general population: 18% versus a prevalence of 9-10%, according to different studies. The mean number of stools per week decreased from 17.59 to 12.83 after treatment (p<0.0001). Before treatment, 54% of patients had watery stools and 46% had smooth stools; at the end of treatment, only 18.5% of patients still had watery stools, and 34% had normal stools. 52% of patients attributed their symptoms to their diet: 34% to vegetables, 29% to fruit, 15% to milk, 15% to fat, 6% to peppers and spices, and 4% to sugar. CONCLUSION: This observational investigation shed new light on patients with IBS-D, the HRQOL of which is altered by a fecal incontinence rate twice as high as that of the general population. Correlation with diet is confirmed by 1 out of 2 patients reporting poor tolerance of fiber and dairy products. Nutritional management should thus be part of these patients' treatment. Inactivated Lactobacillus LB plus fermented culture medium is a probiotic drug that has been used by physicians for a long time to treat patients with diarrhea. Strongly concentrated, it has no side effects and seems to help these patients. Due to a strong placebo effect in patients with this pathology, however, a controlled study is necessary to confirm this result.

Challenges and solutions for the identification of membrane proteins in non-model plants.

The workhorse for proteomics in non-model plants is classical two-dimensional electrophoresis, a combination of iso-electric focusing and SDS-PAGE. However, membrane proteins with multiple membrane spanning domains are hardly detected on classical 2-DE gels because of their low abundance and poor solubility in aqueous media. In the current review, solutions that have been proposed to handle these two problems in non-model plants are discussed. An overview of alternative techniques developed for membrane proteomics is provided together with a comparison of their strong and weak points. Subsequently, strengths and weaknesses of the different techniques and methods to evaluate the identification of membrane proteins are discussed. Finally, an overview of recent plant membrane proteome studies is provided with the used separation technique and the number of identified membrane proteins listed.

A workflow for peptide-based proteomics in a poorly sequenced plant: a case study on the plasma membrane proteome of banana.

Membrane proteins are an interesting class of proteins because of their functional importance. Unfortunately their analysis is hampered by low abundance and poor solubility in aqueous media. Since shotgun methods are high-throughput and partly overcome these problems, they are preferred for membrane proteomics. However, their application in non-model plants demands special precautions to prevent false positive identification of proteins. In the current paper, a workflow for membrane proteomics in banana, a poorly sequenced plant, is proposed. The main steps of this workflow are (i) optimization of the peptide separation, (ii) performing de novo sequencing to allow a sequence homology search and (iii) visualization of identified peptide-protein associations using Cytoscape to remove redundancy and wrongly assigned peptides, based on species-specific information. By applying this workflow, integral plasma membrane proteins from banana leaves were successfully identified.

Three unrelated sphingomyelin analogs spontaneously cluster into plasma membrane micrometric domains.

Micrometric lipid compartmentation at the plasma membrane is disputed. Using live confocal imaging, we found that three unrelated fluorescent sphingomyelin (SM) analogs spontaneously clustered at the outer leaflet into micrometric domains, contrasting with homogeneous labelling by DiIC18 and TMA-DPH. In erythrocytes, these domains were round, randomly distributed, and reversibly coalesced under hypotonicity. BODIPY-SM and -glucosylceramide showed distinct temperature-dependence, in the same ranking as Tm for corresponding natural lipids, indicating phase behaviour. Scanning electron microscopy excluded micrometric surface structural features. In CHO cells, similar surface micrometric patches were produced by either direct BODIPY-SM insertion or intracellular processing from BODIPY-ceramide, ruling out aggregation artefacts. BODIPY-SM surface micrometric patches were refractory to endocytosis block or actin depolymerization and clustered upon cholesterol deprivation, indicating self-clustering at the plasma membrane. BODIPY-SM excimers further suggested clustering in ordered domains. Segregation of BODIPY-SM and -lactosylceramide micrometric domains showed coexistence of distinct phases. Consistent with micrometric domain boundaries, fluorescence recovery after photobleaching (FRAP) revealed restriction of BODIPY-SM lateral diffusion over long-range, but not short-range, contrasting with comparable high mobile fraction of BODIPY-lactosylceramide in both ranges. Controlled perturbations of endogenous SM pool similarly affected BODIPY-SM domain size by confocal imaging and its mobile fraction by FRAP. The latter evidence supports the hypothesis that, as shown for BODIPY-SM, endogenous SM spontaneously clusters at the plasmalemma outer leaflet of living cells into ordered micrometric domains, defined in shape by liquid-phase coexistence and in size by membrane tension and cholesterol. This proposal remains speculative and calls for further investigations.

Caspase-mediated inhibition of sphingomyelin synthesis is involved in FasL-triggered cell death.

Ceramide can be converted into sphingomyelin by sphingomyelin synthases (SMS) 1 and 2. In this study, we show that in human leukemia Jurkat cells, which express mainly SMS1, Fas ligand (FasL) treatment inhibited SMS activity in a dose- and time-dependent manner before nuclear fragmentation. The SMS inhibition elicited by FasL (1) was abrogated by benzyloxycarbonyl valyl-alanyl-aspartyl-(O-methyl)-fluoromethylketone (zVAD-fmk), a broad-spectrum caspase inhibitor; (2) did not occur in caspase-8-deficient cells and (3) was not affected in caspase-9-deficient cells. Western blot experiments showed SMS1 cleavage in a caspase-dependent manner upon FasL treatment. In a cell-free system, caspase-2, -7, -8 and -9, but not caspase-3 and -10, cleaved SMS1. In HeLa cells, SMS1 was Golgi localized and relocated throughout the cytoplasm in cells exhibiting an early apoptotic phenotype on FasL treatment. zVAD-fmk prevented FasL-induced SMS1 relocation. Thus, FasL-mediated SMS1 inhibition and relocation depend on caspase activation and likely represent proximal events in Fas signaling. FasL-induced ceramide production and cell death were enhanced in cells stably expressing an siRNA against SMS1. Conversely, in cells stably overexpressing SMS1, FasL neither increased ceramide generation nor efficiently induced cell death. Altogether, our data show that SMS1 is a novel caspase target that is functionally involved in the regulation of FasL-induced apoptosis.

Quantitative immunohistochemical expression of c Kit in breast carcinomas is predictive of patients' outcome.

BACKGROUND: c Kit (CD117) expression in tissues has been reported as a relevant target for specific therapy in some human malignancies, but has been poorly documented in breast carcinomas. METHODS: The prognostic significance of c Kit in a series of 924 breast carcinomas (mean follow-up, 79 months) was investigated using standardised high-throughput quantitative densitometry of immunohistochemical precipitates in tissue microarrays. RESULTS: c Kit was expressed in 14.7% breast carcinomas (and in 42 out of 586 node-negative tumours). In univariate analysis, (log-rank test) the score of c Kit expression correlated with poor patient outcome P=0.02 and particularly in node-negative cases (P=0.002). In multivariate Cox analysis, c Kit was an indicator of metastasis independent of 25 other concomitantly evaluated markers of prognosis. Logistic regression showed that c Kit ranked 10 out of 25 (P=0.041), and was included in a 10-marker signature that allowed 79.2% of the patients to be correctly classified in the metastatic or metastasis-free categories independently of hormone receptors and HER-2 status. Interestingly, c Kit was also a significant predictor of metastasis in node-negative tumours (2 out of 25 ranking, P<0.0001) and included in a six-marker signature of prognosis, correctly classifying 88.6% of the patients (P<0.0001). CONCLUSION: We concluded that, as assessed by quantitative immunohistochemistry, c Kit is an independent prognostic indicator that could also potentially serve as a target for specific therapy in breast carcinomas.