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Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas

Gerhard, Rene; Ricardo, Sara; Albergaria, Andre; Gomes, Madalena; Silva, Alfredo Ribeiro; Logullo, Angela Flavia; Cameselle-Teijeiro, Jorge F.; Paredes, Joana; Schmitt, Fernando
Fonte: CHURCHILL LIVINGSTONE; EDINBURGH Publicador: CHURCHILL LIVINGSTONE; EDINBURGH
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
35.76%
Purpose: The claudin-low molecular subtype of breast cancer includes triple negative invasive carcinomas, with a high frequency of metaplastic and medullary features. The aim of this study was to evaluate the immunohistochemistry expression of claudins in a series of metaplastic breast carcinomas. We also assessed other claudin-low features, such as the cancer stem cell-like and epithelial-to-mesenchymal transition phenotypes. Results: The majority of the cases showed weak or negative staining for membrane claudins expression. We found 76.9% (10/13) low expressing cases for claudin-1, 84.6% (11/13) for claudin-3 and claudin-4, and 92.3% (12/13) for claudin-7. Regarding the cancer stem cell marker ALDH1, 30.8% (4/13) showed positive staining. We also showed that the majority of the cases presented a CD44(+)CD24(-/low) phenotype, positivity for vimentin and lack of E-cadherin expression. Interestingly, these claudin-low molecular features were specific of the mesenchymal component of metaplastic breast carcinomas, since its frequency was very low in other breast cancer molecular subtypes, as luminal, HER2-overexpressing and non-metaplastic triple negative tumors. Conclusions: The negative/low expression of claudins and E-cadherin, high levels of vimentin...

Expressão de CD44 e CD24 em carcinomas mamários ductais invasivos de acordo com análise dos subtipos moleculares e sua relação com fatores prognósticos; CD44 and CD24 expression in ductal invasive breast carcinomas, classified by molecular subtypes and its association with prognostic factors

Bernardi, Maria Auxiliadora
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 15/09/2011 PT
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35.98%
Carcinomas de mama são heterogêneos e consistem de diversos tipos celulares. Perfis de expressão gênica usando DNA microarrays identificaram quatro subtipos moleculares fundamentais baseados na expressão de receptores hormonais (estrógeno e progesterona) e de fator de crescimento epidérmico (HER2) (luminal tipo A, luminal tipo B, tumores expressando somente HER2 e triplos negativos) refletindo a heterogeneidade molecular dos carcinomas. Sugeriu-se que esta heterogeneidade advém da presença de células tronco tumorais com a capacidade de se diferenciar ao longo de vias divergentes e outros estudos sugeriram que a presença destas células tronco tumorais pode ser evidenciada pela análise fenotípica de CD44 e CD24. Nosso objetivo foi detectar a freqüência de CD24 e CD44 isolados ou combinados, analisados por imunoistoquímica e sua associação com os subtipos moleculares e com diversos marcadores biológicos em 95 casos de carcinoma ductal infiltrativo organizados em um microarranjo tissular (TMA). Realizamos determinações imunoistoquímicas de CD44, CD24, citoqueratinas (CK5, CK6, CK18), claudina 7 e Ki67. Subgrupos moleculares foram definidos pela expressão imunoistoquímica de RE, RP e HER2. Resultados: Os tumores apresentaram uma maior freqüência dos grupos luminais (49...

Selectivity of Agonists for the Active State of M1 to M4 Muscarinic Receptor Subtypes

Figueroa, Katherine W.; Griffin, Michael T.; Ehlert, Frederick J.
Fonte: American Society for Pharmacology and Experimental Therapeutics Publicador: American Society for Pharmacology and Experimental Therapeutics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
35.9%
We measured the intrinsic relative activity (RAi) of muscarinic agonists to detect possible selectivity for receptor subtypes and signaling pathways. RAi is a relative measure of the microscopic affinity constant of an agonist for the active state of a GPCR expressed relative to that of a standard agonist. First, we estimated RAi values for a panel of agonists acting at the M4 muscarinic receptor coupled to three distinct G-protein pathways: Gi inhibition of cAMP accumulation, Gs stimulation of cAMP accumulation, and Gα15 stimulation of phosphoinositide hydrolysis. Our results show similar RAi values for each agonist, suggesting that the same active state of the M4 receptor triggers the activation of the three G proteins. We also estimated RAi values for agonists across M1 to M4 muscarinic subtypes stably transfected in Chinese hamster ovary cells. Our results show selectivity of McN-A-343 [4-I-[3-chlorophenyl]carbamoyloxy)-2-butynyltrimethylammnonium chloride] for the M1 and M4 subtypes and selectivity of pilocarpine for the M1 and M3 subtypes. The other agonists tested lacked marked selectivity among M1 to M4 receptors. Finally, we estimated RAi values from published literature on M1, M2, and M3 muscarinic responses and obtained results consistent with our own studies. Our results show that the RAi estimate is a useful receptor-dependent measure of agonist activity.

Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach

Scott, Milcah C.; Sarver, Aaron L.; Gavin, Katherine J.; Thayanithy, Venugopal; Getzy, David M.; Newman, Robert A.; Cutter, Gary R.; Lindblad-Toh, Kerstin; Kisseberth, William C.; Hunter, Lawrence E.; Subramanian, Subbaya; Breen, Matthew; Modiano, Jaime F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.99%
The heterogeneous and chaotic nature of osteosarcoma has confounded accurate molecular classification, prognosis, and prediction for this tumor. The occurrence of spontaneous osteosarcoma is largely confined to humans and dogs. While the clinical features are remarkably similar in both species, the organization of dogs into defined breeds provides a more homogeneous genetic background that may increase the likelihood to uncover molecular subtypes for this complex disease. We thus hypothesized that molecular profiles derived from canine osteosarcoma would aid in molecular subclassification of this disease when applied to humans. To test the hypothesis, we performed genome wide gene expression profiling in a cohort of dogs with osteosarcoma, primarily from high-risk breeds. To further reduce inter-sample heterogeneity, we assessed tumor-intrinsic properties through use of an extensive panel of osteosarcoma-derived cell lines. We observed strong differential gene expression that segregated samples into two groups with differential survival probabilities. Groupings were characterized by the inversely correlated expression of genes associated with G2/M transition and DNA damage checkpoint and microenvironment-interaction categories. This signature was preserved in data from whole tumor samples of three independent dog osteosarcoma cohorts...

PAM50 assay and the three-gene model for identifying the major and clinically relevant molecular subtypes of breast cancer

Prat, A.; Parker, J. S.; Fan, C.; Perou, C. M.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.89%
It has recently been proposed that a three-gene model (SCMGENE) that measures ESR1, ERBB2, and AURKA identifies the major breast cancer intrinsic subtypes and provides robust discrimination for clinical use in a manner very similar to a 50-gene subtype predictor (PAM50). However, the clinical relevance of both predictors was not fully explored, which is needed given that a ~30 % discordance rate between these two predictors was observed. Using the same datasets and subtype calls provided by Haibe-Kains and colleagues, we compared the SCMGENE assignments and the research-based PAM50 assignments in terms of their ability to (1) predict patient outcome, (2) predict pathological complete response (pCR) after anthracycline/taxane-based chemotherapy, and (3) capture the main biological diversity displayed by all genes from a microarray. In terms of survival predictions, both assays provided independent prognostic information from each other and beyond the data provided by standard clinical–pathological variables; however, the amount of prognostic information was found to be significantly greater with the PAM50 assay than the SCMGENE assay. In terms of chemotherapy response, the PAM50 assay was the only assay to provide independent predictive information of pCR in multivariate models. Finally...

Targeting the PyMT Oncogene to Diverse Mammary Cell Populations Enhances Tumor Heterogeneity and Generates Rare Breast Cancer Subtypes

Smith, Brittni A.; Shelton, Dawne N.; Kieffer, Collin; Milash, Brett; Usary, Jerry; Perou, Charles M.; Bernard, Philip S.; Welm, Bryan E.
Fonte: SAGE Publications Publicador: SAGE Publications
Tipo: Artigo de Revista Científica
Publicado em /09/2012 EN
Relevância na Pesquisa
35.84%
Human breast cancer is a heterogeneous disease composed of different histologies and molecular subtypes, many of which are not replicated in animal models. Here, we report a mouse model of breast cancer that generates unique tumor histologies including tubular, adenosquamous, and lipid-rich carcinomas. Utilizing a nononcogenic variant of polyoma middle T oncogene (PyMT) that requires a spontaneous base-pair deletion to transform cells, in conjunction with lentiviral transduction and orthotopic transplantation of primary mammary epithelial cells, this model sporadically induces oncogene expression in both the luminal and myoepithelial cell lineages of the normal mouse mammary epithelium. Microarray and hierarchical analyses using an intrinsic subtype gene set revealed that lentiviral PyMT generates both luminal and basal-like tumors. Cumulatively, these results show that low-level expression of PyMT in a broad range of cell types significantly increases tumor heterogeneity and establishes a mouse model of several rare human breast cancer subtypes.

Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes

Prat, Aleix; Karginova, Olga; Parker, Joel S.; Fan, Cheng; He, Xiaping; Bixby, Lisa; Harrell, J. Chuck; Roman, Erick; Adamo, Barbara; Troester, Melissa; Perou, Charles M.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
56.01%
Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly...

Multiclass Prediction with Partial Least Square Regression for Gene Expression Data: Applications in Breast Cancer Intrinsic Taxonomy

Huang, Chi-Cheng; Tu, Shih-Hsin; Huang, Ching-Shui; Lien, Heng-Hui; Lai, Liang-Chuan; Chuang, Eric Y.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
35.95%
Multiclass prediction remains an obstacle for high-throughput data analysis such as microarray gene expression profiles. Despite recent advancements in machine learning and bioinformatics, most classification tools were limited to the applications of binary responses. Our aim was to apply partial least square (PLS) regression for breast cancer intrinsic taxonomy, of which five distinct molecular subtypes were identified. The PAM50 signature genes were used as predictive variables in PLS analysis, and the latent gene component scores were used in binary logistic regression for each molecular subtype. The 139 prototypical arrays for PAM50 development were used as training dataset, and three independent microarray studies with Han Chinese origin were used for independent validation (n = 535). The agreement between PAM50 centroid-based single sample prediction (SSP) and PLS-regression was excellent (weighted Kappa: 0.988) within the training samples, but deteriorated substantially in independent samples, which could attribute to much more unclassified samples by PLS-regression. If these unclassified samples were removed, the agreement between PAM50 SSP and PLS-regression improved enormously (weighted Kappa: 0.829 as opposed to 0.541 when unclassified samples were analyzed). Our study ascertained the feasibility of PLS-regression in multi-class prediction...

Expression of Neuroendocrine Markers in Different Molecular Subtypes of Breast Carcinoma

Wachter, David L.; Hartmann, Arndt; Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander; Bayer, Christian M.; Agaimy, Abbas
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.86%
Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies.

Comparative Multidimensional Molecular Analyses of Pediatric Diffuse Intrinsic Pontine Glioma Reveals Distinct Molecular Subtypes

Saratsis, Amanda M.; Kambhampati, Madhuri; Snyder, Kendall; Yadavilli, Sridevi; Devaney, Joe; Harmon, Brennan; Hall, Jordan; Raabe, Eric H.; An, Ping; Weingart, Melanie; Rood, Brian R.; Magge, Suresh; MacDonald, Tobey J.; Packer, Roger J.; Nazarian, Javad
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
35.81%
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly morbid form of pediatric brainstem glioma. Here, we present the first comprehensive protein, mRNA, and methylation profiles of fresh frozen DIPG specimens (n=14), normal brain tissue (n=10), and other pediatric brain tumors (n=17). Protein profiling identified 2,305 unique proteins indicating distinct DIPG protein expression patterns compared to other pediatric brain tumors. Western blot and immunohistochemistry validated upregulation of Clusterin (CLU), Elongation Factor 2 (EF2), and Talin-1 (TLN1) in DIPGs studied. Comparisons to mRNA expression profiles generated from tumor and adjacent normal brain tissue indicated two DIPG subgroups, characterized by upregulation of Myc (N-Myc) or Hedgehog (Hh) signaling. We validated upregulation of PTCH, a membrane receptor in the Hh signaling pathway, in a subgroup of DIPG specimens. DNA methylation analysis indicated global hypomethylation of DIPG compared to adjacent normal tissue specimens, with differential methylation of 24 genes involved in Hh and Myc pathways, correlating with protein and mRNA expression patterns. Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77% of our DIPG cohort. Supervised analysis revealed a unique methylation pattern in mutated specimens compared to the wild type DIPG samples.

Distinct breast cancer subtypes in women with early-onset disease across races

Singh, Mandeep; Ding, Yi; Zhang, Li-Ying; Song, Dong; Gong, Yun; Adams, Sylvia; Ross, Dara S; Wang, Jin-Hua; Grover, Shruti; Doval, Dinesh Chandra; Shao, Charles; He, Zi-Li; Chang, Victor; Chin, Warren W; Deng, Fang-Ming; Singh, Baljit; Zhang, David; Xu,
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 16/07/2014 EN
Relevância na Pesquisa
35.9%
Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients.

Association between molecular subtypes and lymph node status in invasive breast cancer

Si, Chengshuai; Jin, Yiting; Wang, Hongying; Zou, Qiang
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/09/2014 EN
Relevância na Pesquisa
35.75%
Background: The predictors for the involvement of lymph node (LN) have been widely studied. But the implication of the molecular type has not been well studied. Using the database of our institution, we investigated this relation. Methods: Patients with T1 and T2 primary breast cancer without distant metastasis were included in our study from 2012 Jan to 2013 Dec. All patients undertook the resection of the primary and the axillary lymph nodes (ALNs). We collected the clinical data including age at diagnosis, the status of ER, PR and HER2, tumor size, nodal status, and histological type. The relationship between demographic, tumor characteristics and lymph node status was evaluated. Results: 814 patients were included in our study. The number and the percentage (in parentheses) of each type of breast cancer is as follows: Luminal A 230 (28.3%), Luminal Her2- 284 (34.9%), Luminal Her2+ 104 (12.8%), HER2+ 72 (8.8%), TNBC 124 (15.2%). On univariate and multivariate analysis, tumor size and tumor subtype show statistical significance with LN involvement. Using TNBC as a reference, both Luminal B type (Luminal HER2-, Luminal HER2+) shows significant higher probability of LN involvement. Conclusions: LN involvement is an intrinsic characteristic for molecular subtype of breast cancer. Triple positive and triple negative breast cancer accounts the most and least possibility of LN involvement.

Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition

Roepman, Paul; Schlicker, Andreas; Tabernero, Josep; Majewski, Ian; Tian, Sun; Moreno, Victor; Snel, Mireille H; Chresta, Christine M; Rosenberg, Robert; Nitsche, Ulrich; Macarulla, Teresa; Capella, Gabriel; Salazar, Ramon; Orphanides, George; Wessels, Lo
Fonte: BlackWell Publishing Ltd Publicador: BlackWell Publishing Ltd
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
36.12%
In most colorectal cancer (CRC) patients, outcome cannot be predicted because tumors with similar clinicopathological features can have differences in disease progression and treatment response. Therefore, a better understanding of the CRC biology is required to identify those patients who will benefit from chemotherapy and to find a more tailored therapy plan for other patients. Based on unsupervised classification of whole genome data from 188 stages I–IV CRC patients, a molecular classification was developed that consist of at least three major intrinsic subtypes (A-, B- and C-type). The subtypes were validated in 543 stages II and III patients and were associated with prognosis and benefit from chemotherapy. The heterogeneity of the intrinsic subtypes is largely based on three biological hallmarks of the tumor: epithelial-to-mesenchymal transition, deficiency in mismatch repair genes that result in high mutation frequency associated with microsatellite instability and cellular proliferation. A-type tumors, observed in 22% of the patients, have the best prognosis, have frequent BRAF mutations and a deficient DNA mismatch repair system. C-type patients (16%) have the worst outcome, a mesenchymal gene expression phenotype and show no benefit from adjuvant chemotherapy treatment. Both A-type and B-type tumors have a more proliferative and epithelial phenotype and B-types benefit from adjuvant chemotherapy. B-type tumors (62%) show a low overall mutation frequency consistent with the absence of DNA mismatch repair deficiency. Classification based on molecular subtypes made it possible to expand and improve CRC classification beyond standard molecular and immunohistochemical assessment and might help in the future to guide treatment in CRC patients.

Prognostic Relevance of Circulating Tumor Cells in Molecular Subtypes of Breast Cancer

Banys-Paluchowski, M.; Schneck, H.; Blassl, C.; Schultz, S.; Meier-Stiegen, F.; Niederacher, D.; Krawczyk, N.; Ruckhaeberle, E.; Fehm, T.; Neubauer, H.
Fonte: Georg Thieme Verlag KG Publicador: Georg Thieme Verlag KG
Tipo: Artigo de Revista Científica
Publicado em /03/2015 EN
Relevância na Pesquisa
55.93%
Circulating tumor cells (CTCs) can be detected in the peripheral blood of breast cancer patients with early and metastatic disease. Recent data suggest that immune pathologic characteristics between the primary tumor, metastatic colonies and CTCs are discordant and that CTCs possess an independent phenotype that is associated with prognosis and treatment efficacy. Large scale gene expression analysis has provided the possibility to stratify breast cancer according to the gene expression fingerprint of primary tumor tissue into five intrinsic molecular subtypes which can be associated with different clinical outcome. As a consequence of the different prognostic power of primary tumorsʼ characteristics and CTCs several groups have started to investigate if CTCs might be disseminated differentially within these breast cancer subtypes. They determined the CTC number in immunohistochemical subtypes to validate if CTCs may provide differential and more specific prognostic information within each subtype. This review provides an overview of the outcome of some recently published data gathered from early and metastatic breast cancer.

Characterization of molecular subtypes of Korean breast cancer: An ethnically and clinically distinct population

HAN, WONSHIK; NICOLAU, MONICA; NOH, DONG-YOUNG; JEFFREY, STEFANIE S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/2010 EN
Relevância na Pesquisa
45.93%
We aimed to investigate the molecular characteristics of Korean breast cancer. A cDNA microarray study (>42k clones) was performed on 69 breast cancers and three normal breast tissues. The subjects had a high percentage of HER-2 expression, hormone receptor negativity, and young onset. Molecular subtypes according to gene expression profiles were determined and their correlations to the clinicopathologic characteristics and patients outcome were analyzed. The tumors were subdivided into luminal-, normal breast-like, ERBB2+, and basal-like subtypes according to the correlations to the previously described intrinsic genes and five centroids. Only a few tumors were highly correlated to the luminal B and normal-like centroids. The high grade tumors with high p53 and Ki-67 were found more commonly in non-luminal tumors. Distant recurrence-free survival was worse in ERBB2+ and basal-like subgroups than luminal tumors. In an unsupervised clustering with 864 genes, many interesting gene clusters were observed, some of which had not been previously described. Although the Korean breast cancers showed generally similar molecular phenotypes as Western studies, some distinct gene expression patterns and their association to clinical outcomes were observed.

Subtipos clínico-patológicos de carcinoma de mama e sua relação com a expressão da COX2 e da p53 = : Clinico-pathological subtypes of breast cancer related to COX2 and p53; Clinico-pathological subtypes of breast cancer related to COX2 and p53

Kátia Piton Serra
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 23/05/2014 PT
Relevância na Pesquisa
36.04%
Introdução: Na última década, doferentes subtipos moleculares de cancer de mama foram propostos. A classificação clinic-patológicas dos subtipos vem comprovando ser estratégica para predizer sobrevida e resposta ao tratamento. Modificação recente da classificação considera a avaliação semiquantitativa da expressão dos RP no curso clínico e resposta ao tratamento. Embora exista associação apreciável com o prognóstico e indicação de terapia citotóxica e endócrina, os subtipos parecem falhar em explicar completamente o comçortamento da doença e a resposta ao tratamento. Moléculas como as da família das cicloxigenases (COX), composta por três entidades (COX 1, 2 e 3) vem demonstrando associação com a carcinogênese mamária, e a análise da expressão da p53 nos tumores de mama pode também oferecer informações adicionais para determinação do prognóstico. Objetivos: Foi avaliada a associação entre os subtipos clinic-patológicos do cancer de mama com o prognóstico e fatores preditivos em uma relativamente grande casuística de pacientes Brasileiras com câncer de mama, que foram acompanhadas por cerca de quatro anos. Foram discutidas as vantagens e possíveis ressalvas relacionadas à nova classificação. Também foi mensurada a expressão da COX2 e da p53 em relação aos subtipos clínico-patológicos e avaliada se a expressão destas molécular poderia explicar a variabilidade no prognóstico ainda encontrada entre os subtipos clínico-patológicos do câncer de mama. Metodologia: Um total de 183 amostras de cancer de mama foram obtidas de mulheres tratadas no Hospital da Mulher da Universidade Estadual de Campinas...

A Supervised Network Analysis on Gene Expression Profiles of Breast Tumors Predicts a 41-Gene Prognostic Signature of the Transcription Factor MYB across Molecular Subtypes

Liu, Li-Yu D.; Chang, Li-Yun; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Chang, King-Jen; Hsieh, Fon-Jou
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
35.78%
Background. MYB is predicted to be a favorable prognostic predictor in a breast cancer population. We proposed to find the inferred mechanism(s) relevant to the prognostic features of MYB via a supervised network analysis. Methods. Both coefficient of intrinsic dependence (CID) and Galton Pierson's correlation coefficient (GPCC) were combined and designated as CIDUGPCC. It is for the univariate network analysis. Multivariate CID is for the multivariate network analysis. Other analyses using bioinformatic tools and statistical methods are included. Results. ARNT2 is predicted to be the essential gene partner of MYB. We classified four prognostic relevant gene subpools in three breast cancer cohorts as feature types I–IV. Only the probes in feature type II are the potential prognostic feature of MYB. Moreover, we further validated 41 prognosis relevant probes to be the favorable prognostic signature. Surprisingly, two additional family members of MYB are elevated to promote poor prognosis when both levels of MYB and ARNT2 decline. Both MYBL1 and MYBL2 may partially decrease the tumor suppressive activities that are predicted to be up-regulated by MYB and ARNT2. Conclusions. The major prognostic feature of MYB is predicted to be determined by the MYB subnetwork (41 probes) that is relevant across subtypes.

Geographic differences in the distribution of molecular subtypes of breast cancer in Brazil

Carvalho, Filomena M; Bacchi, Lívia M; Pincerato, Kátia M; Van de Rijn, Matt; Bacchi, Carlos E
Fonte: BMC Publicador: BMC
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
86.14%
Abstract Background To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. Methods The study was retrospective observational. We classified 5,687 invasive breast cancers by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2- positive), and triple-negative (TN) (ER negative, PR negative, and HER2- negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. Results South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative)...

Geographic differences in the distribution of molecular subtypes of breast cancer in Brazil

Carvalho, Filomena M; Bacchi, Lívia M; Pincerato, Kátia M; Van de Rijn, Matt; Bacchi, Carlos E
Fonte: Biblioteca Digital da Produção Intelectual da USP Publicador: Biblioteca Digital da Produção Intelectual da USP
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
56.03%
Abstract Background To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. Methods The study was retrospective observational. We classified 5,687 invasive breast cancers by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2- positive), and triple-negative (TN) (ER negative, PR negative, and HER2- negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. Results South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative)...

Phenotypic and molecular characterization of the intrinsic molecular subtypes of breast cancer

Prat Aparicio, Aleix
Fonte: Bellaterra : Universitat Autònoma de Barcelona, Publicador: Bellaterra : Universitat Autònoma de Barcelona,
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em //2014 ENG; ENG
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46.22%
La implementación de programas de cribaje y/o de prevención junto a terapias innovadoras está disminuyendo la mortalidad por cáncer de mama. Ahora bien, más de 120.000 muertes anuales ocurren en Estados Unidos y en Europa por esta causa. Una explicación de este hecho es que aún nos falta obtener una fotografía completa de la heterogeneidad biológica del cáncer de mama con respeto a sus alteraciones moleculares, sensibilidad al tratamiento, y composición celular. De hecho, esta complejidad no se halla reflejada por los principales parámetros clínicos (edad, afectación ganglionar, tamaño tumoral, grado histológico) o los marcadores patológicos (receptor de estrógeno [ER], progesterona [PR] y el receptor del factor de crecimiento epidérmico tipo 2 [HER2]), los cuales están siendo utilizados hoy en día en la clínica para estratificar las pacientes en grupos pronósticos y/o terapéuticos. Los estudios basados en expresión global de genes han proporcionado una mayor comprensión de este escenario tan complejo. Durante los últimos 10 años, seis subtipos moleculares de cáncer de mama (Luminal A, Luminal B, HER2-enriched, Claudin-low, Normal Breast-like and Basal-like) han sido identificados y estudiados extensamente. Conocidos como los subtipos intrínsecos...