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ABSTRACT: The introduction of the benchtop massive parallel sequencers made it possible, for the majority of clinical diagnostic laboratories, to gain access to this fast evolving technology. In this study, using the Ion Torrent PGM, we present a strategy for the molecular diagnosis of hereditary breast and ovarian cancer and respective analytical validation. The methodology relies on a multiplex PCR amplification of the BRCA1 and BRCA2 genes combined with a variant prioritization pipeline, designed to minimize the number of false positive calls without the introduction of false negative results. A training set of samples was used to optimize the entire process and a second set was used to validate and independently evaluate the performance of the workflow. Performing the study in a blind manner relative to the variants in the samples and using conventional Sanger sequencing as standard, the workflow resulted in a strategy with a maximum analytical sensitivity ≥98.6% with a confidence of 95% and a specificity of 96.9%. Importantly, no true variant was missed. This study presents a comprehensive MPS-Sanger sequencing based strategy, which results in a high analytical sensitivity assay that provides a time- and cost-effective strategy for the identification of mutations in the BRCA1 and BRCA2 genes.
Human Mutation 01/2013; · 5.69 Impact Factor
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ABSTRACT: P-cadherin is a cell-cell adhesion molecule codified by the CDH3 gene, which expression is highly associated with undifferentiated cells in normal adult epithelial tissues, as well as with poorly differentiated carcinomas. In breast cancer, P-cadherin is frequently overexpressed in high-grade tumours and is a well-established indicator of aggressive tumour behaviour and poor patient prognosis. However, till now, the mechanisms controlling CDH3 gene activation have been poorly explored. Since we recently described the existence of several CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor binding sites at the CDH3 promoter, the aim of this study was to assess if the distinct C/EBPβ isoforms were directly involved in the transcriptional activation of the CDH3 gene in breast cancer cells. DNA-protein interactions, mutation analysis and luciferase reporter assay studies have been performed. We demonstrated that C/EBPβ is co-expressed with P-cadherin in breast cancer cells and all the three isoforms function as transcriptional regulators of the CDH3 gene, directly interacting with specific regions of its promoter. Interestingly, this transcriptional activation was only reflected at the P-cadherin protein level concerning the LIP isoform. Taken together, our data show that CDH3 is a newly defined transcriptional target gene of C/EBPβ isoforms in breast cancer, and we also identified the binding sites that are relevant for this activation.
PLoS ONE 01/2013; 8(2):e55749. · 4.09 Impact Factor
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ABSTRACT: Cynara cardunculus (Cc) is a multipurpose species; beyond its use in southwestern European cuisine, it is also used for the production of solid biofuel, seed oil, biodiesel, paper pulp and cheese, as well as animal feed. In addition, Cc has a long tradition of use in folk medicine as a diuretic and liver protector. The value of this species as a source of bioactive compounds is known; however, pharmacological use would further increase its cultivation. The main goal of the current work was to evaluate the potential of Cc as source of anti-carcinogenic phytochemicals. Different methanolic extracts obtained from wild and cultivated plants were tested for antioxidant activity and effect on breast OPEN ACCESS Agriculture 2012, 2 473 tumor cell viability. The most effective extract, both as antioxidant and inhibition of tumor cell viability, was tested for effects on angiogenesis and tumor cell migration capacity. All the extracts tested had high antioxidant activity; however, only green leaves and dry head extracts exhibit anti-proliferative activity. Green cultivated leaves (GCL) were the most effective extract both as antioxidant and inhibiting the proliferation of tumor cells; it is equally active inhibiting tumor cell migration and in vivo angiogenesis. GCL extract is an effective inhibitor of several key points in tumor development and thus a promising source of anti-carcinogenic phytochemicals.
Agriculture. 12/2012;
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ABSTRACT: At present, p63, TTF-1, and Napsin-A are the main immunochemical markers used to distinguish squamous cell carcinoma (SCC) from lung adenocarcinoma (ADC). However, studies using antibodies against p63 have demonstrated false-positive results with positivity in some ADC. In contrast, the expression of one of the p63 isoforms (ΔNp63), detected by the antibody p40, is highly specific for SCC. Since most cases of lung cancer are diagnosed in small specimens (cytology/biopsies) and saving material for molecular analysis is mandatory, we recommended the use of p40 (in adjunct with TTF-1 and/or Napsin-A) as the best approach to discriminate SCC and lung ADC. In this paper, we review the physiological and pathological role of p63 isoforms as well as their use as diagnostic markers in lung SCC.
Acta cytologica 12/2012; 57(1):1-8. · 0.49 Impact Factor
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Ana Sofia Ribeiro,
Bárbara Sousa,
Laura Carreto,
Nuno Mendes,
Ana Rita Nobre,
Sara Ricardo,
André Albergaria,
Jorge F Cameselle-Teijeiro,
Rene Gerhard,
Ola Söderberg,
Raquel Seruca,
Manuel A Santos, Fernando Schmitt,
Joana Paredes
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ABSTRACT: P-cadherin overexpression is associated with worse breast cancer survival, being a prognostic marker, as well as a putative therapeutic target for the aggressive triple-negative and basal-like carcinomas (TNBC). Previously, we have shown that P-cadherin promotes breast cancer invasion of cells where membrane E-cadherin was maintained; however, it suppresses invasion in models without endogenous cadherins, like melanomas. Here, we investigated if P-cadherin expression would interfere with the normal adhesion complex and which were the cellular/molecular consequences, constituting, in this way, a new mechanism by which E-cadherin invasive-suppressor function was disrupted. Using breast TNBC models, we demonstrated, for the first time, that P-cadherin co-localizes with E-cadherin, promoting cell invasion due to the disruption caused in the interaction between E-cadherin and cytoplasmic catenins. P-cadherin also induces cell migration and survival, modifying the expression profile of cells expressing wild-type E-cadherin and contributing to alter their cellular behavior. Additionally, E- and P-cadherin co-expressing cells significantly enhanced in vivo tumor growth, compared with cells expressing only E- or only P-cadherin. Finally, we still found that co-expression of both molecules was significantly correlated with high-grade breast carcinomas, biologically aggressive and with poor patient survival, being a strong prognostic factor in this disease. Our results show a role for E- and P-cadherin co-expression in breast cancer progression and highlight the potential benefit of targeting P-cadherin in the aggressive tumors expressing high levels of this protein. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology 11/2012; · 6.32 Impact Factor
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ABSTRACT: AIMS: CD44, CD24 and ALDH1 are the most consistently used biomarkers to identify and characterise the breast cancer stem cell (CSC) phenotype. However, most studies performed until now analysed samples of invasive ductal carcinomas of no special type (IDC-NST). Therefore, prevalence and clinical significance of these CSC markers in breast carcinomas of special histological types (SHT) is largely unknown. For that reason, this study aims to determine the distribution of the breast CD44, CD24 and ALDH1 CSC markers among a series of invasive breast carcinomas of SHT, in comparison with a series of IDC-NST. METHODS: 117 invasive SHT breast carcinomas were analysed for the expression of CD44, CD24 and ALDH1, by immuhohistochemistry. The distribution of these CSC markers was evaluated among the distinct histological special types, and the results were compared with a series of 466 IDC-NST. RESULTS: The expression prevalence of the breast CSC markers differed between special types and IDC-NST. Medullary, papillary and tubular carcinomas were enriched in the CSC phenotype CD44(+)/CD24(-/low) (80.0%, 100.0% and 100.0%, respectively, vs 45.3% in IDC-NST). Considering the ALDH1 cytoplasmic tumour expression, only medullary and metaplastic carcinomas displayed significant increase in CD44(+)/CD24(-/low)/ALDH1(+) CSC phenotype frequency (36.4% and 28.6%, respectively, vs 4.8% in IDC-NST). CONCLUSIONS: The expression distribution of breast CSC markers is largely dependent on histological type. Interestingly, within the distinct SHT, medullary and metaplastic carcinomas are the two types highly associated with high-grade carcinomas, basal-like and claudin-low molecular subtypes, and to the CSC phenotype CD44(+)/CD24(-/low)/ALDH1(+).
Journal of clinical pathology 10/2012; · 2.43 Impact Factor
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ABSTRACT: Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a targeted therapy, the most aggressive tumours still lack a molecular target. Despite vitamin D being classically associated with the physiological role of calcium regulation and phosphate transport in bone metabolism, several studies have demonstrated a wide range of functions for this hormone, which are particularly important in the field of cancer. The mechanisms underlying the protective actions of vitamin D in cancer development are only sparsely understood, but evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. In addition, it has been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. Most of vitamin D biological actions are mediated by the vitamin D receptor and the synthesis and catabolism of this hormone are regulated by the enzymes CYP27B1 and CYP24A1. In the present review we highlight research data concerning the function of this hormone in the mammary gland, with a special focus on breast carcinogenesis. Hence, and although the available data are controversial, we consider not only updated information on the epidemiology of vitamin D in breast cancer and its potential value as a therapeutic agent or prophylactic (with an emphasis on molecular mechanisms and effectors of vitamin D action), but include data on its role in other stages of breast cancer progression as well. Accordingly, we review data on the influence of vitamin D in the development of normal breast and the expression of vitamin D-related proteins (VDR, CYP27B1 and CYP24A21) in benign mammary lesions and ductal carcinomas in situ.
Breast cancer research: BCR 05/2012; 14(3):211. · 5.24 Impact Factor
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Joana Paredes,
Joana Figueiredo,
André Albergaria,
Patrícia Oliveira,
Joana Carvalho,
Ana Sofia Ribeiro,
Joana Caldeira,
Angela Margarida Costa,
Joana Simões-Correia,
Maria José Oliveira, [......],
Salomé S Pinho,
Rita Mateus,
Celso A Reis,
Marina Leite,
Maria Sofia Fernandes, Fernando Schmitt,
Fátima Carneiro,
Céu Figueiredo,
Carla Oliveira,
Raquel Seruca
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ABSTRACT: E-cadherin and P-cadherin are major contributors to cell-cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes during development, and in maintaining integrity and homeostasis in adult tissues. It is now generally accepted that alterations in these two molecules are observed during tumour progression of most carcinomas. Genetic or epigenetic alterations in E- and P-cadherin-encoding genes (CDH1 and CDH3, respectively), or alterations in their proteins expression, often result in tissue disorder, cellular de-differentiation, increased invasiveness of tumour cells and ultimately in metastasis. In this review, we will discuss the major properties of E- and P-cadherin molecules, its regulation in normal tissue, and their alterations and role in cancer, with a specific focus on gastric and breast cancer models.
Biochimica et Biophysica Acta 05/2012; 1826(12):297-311. · 4.66 Impact Factor
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ABSTRACT: The identification and characterization of cancer stem cells might lead to more effective control of neoplastic disease, by directing therapies to the most aggressive cells. For that reason, the identification of cancer stem cells (CSCs) in breast tumours is one of the priorities in breast cancer research, which has resulted in many studies attempting to identify their presence based on the expression of specific molecular markers. In this review, we describe the main molecular markers that have been identified as being able to recognise CSCs in breast carcinomas, the major molecular pathways that regulate CSCs and their association with the different molecular subtypes.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2012; 460(6):545-53. · 2.49 Impact Factor
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ABSTRACT: Class IA phosphoinositide-3’-kinases (PI3Ks) regulate many cellular processes. Despite a clear implication of PI3K in cancer,
the involvement of each of its isoforms namely p110α and p110β in the development of breast cancer remains elusive. Until
recently, the spotlight was given to the α subunit; however, the p110β isoform has now emerged as an interesting target as
well. In order to determine the importance of both these subunits in breast cancer, we aimed to study the expression of p110α
and p110β in a series of invasive breast carcinomas. We constructed tissue microarrays from 315 invasive breast carcinomas
and performed immunohistochemistry for p110α and β, correlating the expression patterns with clinicopathological parameters.
Furthermore, overall survival was analysed through Kaplan–Meier survival curves and Cox regression. We found that p110 subunits
are expressed in 23.8% of invasive breast carcinomas, of which 11.8% express p110α and 15.2% p110β. The p110α positive tumours
correlated with hormone receptor (HR) expression, and were not associated with overall survival. The membrane expression of
p110β was associated with worse prognosis. This was due to its link to HER2-overexpression, lower age of onset, higher grade,
lymph node involvement, distant metastasis and was inversely associated with HR status. Furthermore, p110β expression was
associated with worse overall survival. Importantly our results indicate a role for the beta subunit in the development/progression
of HER2-overexpressing tumours, highlighting possible therapeutic associations between HER2 and p110β inhibitors.
KeywordsPI3K-p110α-p110β-HER2-Breast cancer
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2012; 456(3):235-243. · 2.49 Impact Factor
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André Filipe Vieira,
Sara Ricardo,
Matthew Paul Ablett,
Maria Rita Dionísio,
Nuno Mendes,
André Albergaria,
Gillian Farnie,
Renê Gerhard,
Jorge F Cameselle-Teijeiro,
Raquel Seruca, Fernando Schmitt,
Robert B Clarke,
Joana Paredes
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ABSTRACT: Although the luminal progenitor cell of the normal mammary gland hierarchy has been proposed as the cell-of-origin for basal-like breast cancers, finding the cancer stem cell (CSC) phenotype for this malignancy has proven a difficult task, mostly due to the lack of specific markers. Recently, basal-like sporadic and familial cases of breast cancer have been linked to BRCA1 gene inactivation, which enables the upregulation of the target-repressed CDH3/P-cadherin gene, an important biomarker of basal-like breast carcinomas. Previously, we demonstrated that P-cadherin overexpression can mediate aggressive behavior in these tumors. Thus, our aim was to test whether P-cadherin mediates stem cell properties in basal-like breast carcinomas. Using a series of breast cancer cell lines and primary tumors, we showed that P-cadherin was directly associated with the expression of the breast stem markers CD44, CD49f, and aldehyde dehydrogenase 1 in the basal subtype. Moreover, cell population enriched for P-cadherin expression comprised increased in vitro mammosphere-forming efficiency and capacity to grow colonies in three-dimensional cultures as well as greater tumorigenicity. Importantly, an association was found with stem-/progenitor-like phenotypes of the breast, including the luminal progenitor population, CD49f(+) CD24(+). Additionally, P-cadherin expression conferred resistance to x-ray-induced cell death, sustaining a role for this molecule in another stem cell property. In summary, we demonstrated, for the first time, that P-cadherin mediates stem cell properties, which could be explored in order to better define the CSC phenotype of basal-like breast tumors and the cell-of-origin of this malignancy.
Stem Cells 03/2012; 30(5):854-64. · 7.78 Impact Factor
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ABSTRACT: Apocrine differentiation occurs in a variety of breast lesions, both benign and malignant. This review is a reflection of our critical view of the recent advances towards the understanding of this particular type of breast lesions. Focus is given to the histological criteria that allow their reproductive identification, with additional attention to the recent microarray studies. These describe the recent molecular classification of breast cancer and identify an apocrine molecular subtype that opens the door for new putative therapies for this particular type of tumor. Indeed we anticipate that the determination of androgen receptor will enter into the routine assessment of breast cancer cases and become a surrogate marker for treatment in apocrine triple-negative breast cancer.
Expert Review of Anti-infective Therapy 02/2012; 12(2):215-21. · 2.65 Impact Factor
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ABSTRACT: The triple-negative subgroup of breast cancer includes a cluster of tumors exhibiting low E-cadherin expression (metaplastic carcinomas). In several cancer models, 1 alpha,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)) induces differentiation by increasing E-cadherin expression. The Vitamin D receptor (VDR) was evaluated as a possible therapeutic target for metaplastic carcinomas and 1α,25(OH)(2)D(3) effects as a differentiating agent in triple-negative breast cancer cells were assessed.
Metaplastic carcinomas were assessed for VDR expression by immunohistochemistry; differences in E-cadherin expression in triple-negative breast cancer cells were evaluated by real-time PCR, western blotting and Cadherin 1 (CDH1) methylation status.
Most of the metaplastic carcinomas were positive for VDR expression. Furthermore, 1α,25(OH)(2)D(3) promoted differentiation of MDA-MB-231 cells by inducing de novo E-cadherin expression, an effect that was time- and dose-dependent. Also, E-cadherin expression was due to promoter demethylation.
Metaplastic carcinomas may respond to 1α,25(OH)(2)D(3), since they express VDR and 1α,25(OH)(2)D(3) induces de novo E-cadherin expression in breast cancer cells by promoter demethylation.
Anticancer research 01/2012; 32(1):249-57. · 1.73 Impact Factor
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ABSTRACT: Cadherin-catenin adhesion complexes play important roles by providing cell-cell adhesion and communication in different organ systems. Abnormal expression of cadherin adhesion molecules constitutes a common phenomenon in canine mammary cancer and has been frequently implicated in tumour progression. This paper summarizes the current knowledge on cadherin/catenin adhesion molecules (E-cadherin, β-catenin, and P-cadherin) in canine mammary cancer, focusing on the putative biological functions and clinical significance of these molecules in this disease. This paper highlights the need for further research studies in this setting in order to elucidate the role of these adhesion molecules during tumour progression and metastasis.
Veterinary medicine international. 01/2012; 2012:357187.
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ABSTRACT: The routine use of ancillary studies is reshaping the practice of cytopathology. Currently, most cytopathologists recognize the importance of immunocytochemistry and molecular techniques as adjuncts to morphology to achieve a precise diagnosis. Cytopathologists also are expected to include specific prognostic and predictive information in their reports. The objective of this review was to address the use of immunocytochemistry and molecular techniques to refine the preoperative diagnosis and classification of lung cancer, thyroid cancer, kidney cancer, gastrointestinal cancer, and soft tissue tumors. Fine-needle aspiration also offers a suitable alternative to biopsy in a variety of clinical settings, in particular, when it may be useful to obtain material to study prognostic and predictive markers. This is particularly relevant to obtain material from metastatic sites. The study of KRAS in colon cancer, CKIT in gastrointestinal stromal tumors, and epidermal growth factor receptor mutational status in lung cancer also are addressed particularly in this report.
Cancer Cytopathology 11/2011; 120(3):145-60. · 3.33 Impact Factor
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ABSTRACT: The study of CD44/CD24 and ALDH1 expression is the most accurate method to identify cancer stem cells (CSC) from breast cancer populations. However, the overlap between CD44(+)CD24(-/low) and ALDH1(high) CSC phenotypes in breast cancer seems to be very small, as well as their distribution among intrinsic breast cancer subtypes. Due to this discrepancy, it is imperative to improve the understanding of breast CSC marker distribution.
466 invasive breast carcinomas and eight breast cancer cell lines were analysed for the expression of CD44, CD24 and ALDH1, to evaluate their distribution among the distinct molecular subtypes.
Basal-like tumours (76.5%) contained the higher percentage of cells with the CSC phenotype CD44(+)CD24(-/low) (p<0.0001). From ALDH1-positive cases, 39.4% were also basal-like tumours (p<0.0001). The analysis of breast cancer cell lines indicated that luminal cell lines are mainly enriched in a CD44(-/low)CD24(+) cell population, basal/mesenchymal breast cancer cell lines are enriched in the CD44(+)CD24(-/low) phenotype, whereas the remaining basal/epithelial cell lines are mainly positive for both markers. ALDH1 activity was mainly found in HER-OE and basal/epithelial breast cancer cell.
CD44(+)CD24(-/low) and ALDH1(+) phenotypes seem to identify CSC with distinct levels of differentiation. It seems that the paramount method and biomarkers that identify breast CSC within the distinct molecular subtypes need to be better explored, because it is pivotal to translate the CSC concept to clinical practice. In the future, the recognition of reliable markers to distinguish the CSC pool in each molecular subtype will be decisive for the development of specific target therapies.
Journal of clinical pathology 06/2011; 64(11):937-46. · 2.43 Impact Factor
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ABSTRACT: Antimicrobial peptides (AMPs) are part of the innate immune system and are generally defined as cationic, amphipathic peptides, with less than 50 amino acids, including multiple arginine and lysine residues. The human cathelicidin antimicrobial peptide LL37 can be found at different concentrations in many different cells, tissues and body fluids and has a broad spectrum of antimicrobial and immunomodulatory activities. The healing of wound is a complex process that involves different steps: hemostasis, inflammation, remodeling/granulation tissue formation and re-epithelialization. Inflammation and angiogenesis are two fundamental physiological conditions implicated in this process. We have recently developed a new method for the expression and purification of recombinant LL37. In this work, we show that the recombinant peptide P-LL37 with a N-terminus proline preserves its immunophysiological properties in vitro and in vivo. P-LL37 neutralized the activation of macrophages by lipopolysaccharide (LPS). Besides, the peptide induced proliferation, migration and tubule-like structures formation by endothelial cells. Wound healing experiments were performed in dexamethasone-treated mice to study the effect of LL37 on angiogenesis and wound regeneration. The topical application of synthetic and recombinant LL37 increased vascularization and re-epithelialization. Taken together, these results clearly demonstrate that LL37 may have a key role in wound regeneration through vascularization.
Peptides 06/2011; 32(7):1469-76. · 2.43 Impact Factor
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ABSTRACT: The sentinel lymph node (SLN) is the first lymph node to receive the lymphatic drainage of a primary tumour; based on the knowledge that CK19 is positive in more than 95% of breast carcinomas, a molecular method for intraoperative diagnosis of SLN metastases (the one-step nucleic acid amplification (OSNA) assay) was developed.
To evaluate CK19 immunoreactivity in a series of special histological types of breast carcinoma in order to verify whether the OSNA assay can be used in all breast cancer cases independently of the histological type.
116 samples of invasive breast carcinomas of special type were investigated for CK19 immunoreactivity in tissue microarrays (TMA); negative cases were evaluated in the entire tissue tumour tissue.
Of the 116 cases, 88.9% were positive CK19. Micropapillary and apocrine carcinomas were all positive for CK19 in TMAs. The tubular (93%), mucinous (86%), medullary typical and atypical (84%), mixed carcinomas (83%) increased the rate of positivity for this marker to 100% after repeating the immunostain in whole tissue of negative TMA cases, because the expression of those cases was focal.
Most breast cancer cases were positive for CK19, independent of the histological type; therefore the OSNA assay can be used in all breast cancer cases with a potential low rate of false negative for CK19 detection of micrometastasis. There is an important variation between the positivity assessed on TMAs and the entire tissue; these findings can be clinically relevant because in some cases CK19 is evaluated on core-needle biopsy prior to surgery.
Journal of clinical pathology 03/2011; 64(6):493-7. · 2.43 Impact Factor
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ABSTRACT: The current system of pathologic classification of human breast cancers does not take into account the biologic determinants of prognosis, nor is there a consensus regarding the progression from in situ to invasive carcinoma. The present study compared the molecular phenotypes of in situ and invasive components of breast cancer in the same sample. We built a series of 189 in situ and invasive carcinomas using tissue microarrays and classified them according to their immunoprofiles regarding estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, epidermal growth factor receptor, cytokeratin 5, P-cadherin, and the antigen Ki-67 into luminal A and B, human epidermal growth factor receptor 2 overexpressing, and basal-like carcinomas. We also correlated the subgroups of carcinomas with some of the classical prognostic factors such as histologic grade, tumor size, and lymph node metastasis, as well as with the age of the patient at diagnosis. The overall concordance on the molecular phenotypes between in situ and invasive components was 94%. For the in situ component, 63% of the cases were luminal A; 15%, luminal B; 12%, human epidermal growth factor receptor 2 overexpressing; and 7%, basal-like. Regarding the invasive component, 61% of the cases were luminal A; 16%, luminal B; 12%, human epidermal growth factor receptor 2 overexpressing; and 8%, basal-like. The present study allowed the identification of different immunoprofiles of in situ and invasive breast carcinomas using a specific panel of biomarkers and showed that in most cases, there is a concordance between in situ and invasive component profiles, supporting the theory of parallel disease in breast tumorigenesis.
Human pathology 03/2011; 42(10):1438-46. · 3.03 Impact Factor
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ABSTRACT: A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a "triple-negative" phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication.
The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer.
We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are equally important to stratify different survival outcomes in non-TNBC as in TNBC. We also showed that the NPI retains the ability to stratify and predict survival of TNBC patients.
The importance of this study relies on the need of prognostication improvements on TNBC, showing, at a clinical standpoint, that Nottingham Prognostic Index is as a truthful prognostic tool in TNBC.
BMC Cancer 01/2011; 11:299. · 3.01 Impact Factor
