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Breast cancer progression and metastasis involve the action of multiple transcription factors in tumors and in the cells of the tumor microenvironment (TME) and understanding how these transcription factors are coordinated can guide novel therapeutic strategies. Myocardin related transcription factors A and B (MRTFA/B) are two related transcription factors that redundantly control cancer cell invasion and metastasis in mouse models of breast cancer, but their roles in human cancer are incompletely understood. Here, we used a combination of multiplexed immunofluorescence and bioinformatics analyses to show that MRTFA/B are concurrently activated in tumor cells, but they show distinct patterns of expression across different histological subtypes and in the TME. Importantly, MRTFA expression was elevated in metastatic tumors of African American patients, who disproportionately die from breast cancer. Interestingly, in contrast to publicly available mRNA expression data, MRTFA was similarly expressed across estrogen receptor (ER) positive and negative breast tumors, while MRTFB expression was highest in ER+ breast tumors. Furthermore, MRTFA was specifically expressed in the perivascular antigen presenting cells (APCs) and its expression correlated with the expression of the immune checkpoint protein V-set immunoregulatory receptor (VSIR). These results provide unique insights into how MRTFA and MRTFB can promote metastasis in human cancer, into the racial disparities of their expression patterns, and their function within the complex breast cancer TME.
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PURPOSE: TTC-352 is a selective human estrogen receptor (ER) partial agonist developed for treatment of hormone-refractory ER + breast cancer. METHODS: This was an accelerated dose escalation study with the primary endpoint of maximum tolerated dose that evaluated five dose levels of TTC-352 in breast cancer progressing after at least two lines of hormonal therapy including one in combination with a CDK4/6 inhibitor. The secondary objectives were to determine treatment tolerability, pharmacokinetics of TTC-352, best response, progression-free survival (PFS), and PKCα expression in tumors. RESULTS: The study enrolled 15 patients. No dose-limiting toxicity was observed. Patients experienced the following grade 3 toxicities: asymptomatic pulmonary embolism, diarrhea, aspartate transaminase elevation, and myalgia, and one grade 4 toxicity of gamma glutamyltransferase elevation. Pharmacokinetic half-life was 7.6-14.3 h. The intra- and inter-individual variability for AUC0-∞ hampered assessment of the relationship between dose and AUC0-∞. Median PFS was 58 days (95% CI = 28,112). Higher PKCα expression in tumor stroma was associated with a trend toward longer PFS. CONCLUSIONS: TTC-352 demonstrates safety and early clinical evidence of antitumor activity against heavily pretreated hormone-refractory breast cancer. Based upon TTC-352 plasma concentrations and tolerability, the 180 mg twice a day is recommended for further testing. (ClinicalTrials.gov Identifier: NCT03201913).
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Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina , Feminino , Humanos , Dose Máxima Tolerável , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
A cyst in the breast containing a thick wall, internal septations, or a solid intracystic component is defined as a complex solid and cystic breast mass. These lesions carry a malignant potential between 23-31% and thus require further evaluation with biopsy [1]. We report six cases in which patients were found to have a complex solid and cystic mass, all of which were proven to be malignant breast cancers of varying etiologies. We also review the literature on malignant etiologies of complex solid and cystic breast masses, including their clinical presentation, work-up, histopathologic and immunochemistry findings, treatment, and prognosis.
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Neoplasias da Mama/diagnóstico por imagem , Carcinoma in Situ/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Idoso , Biópsia com Agulha de Grande Calibre , Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia Doppler em Cores , Ultrassonografia MamáriaRESUMO
Composite neoplasms (CNs) are rare and diagnostically challenging lesions that require differentiating between mixed clonal tumors with divergent phenotypes (MT), collision of 2 independent tumors adjacent to each other (CT), and tumor-to-tumor metastasis (TTM). To that end, pathologists have traditionally used immunohistochemistry and limited molecular studies, such as Sanger sequencing. Herein we evaluate the potential application of NGS in the differential diagnosis of these rare neoplasms. Four CNs were included in the study. Two were diagnosed as MT (mixed adenoneuroendocrine carcinoma of the gallbladder and metastatic papillary thyroid carcinoma with squamous dedifferentiation) and 2 were interpreted as TTM (esophageal adenocarcinoma to lung adenocarcinoma and small cell carcinoma of the lung to meningeal melanoma). Diagnoses were made using clinical, histologic, and immunophenotypic information, with the aid of limited molecular studies in 2 cases. Formalin-fixed, paraffin-embedded tissue was dissected for DNA and RNA extraction, and NGS was performed using the Oncomine Comprehensive Panel. The 2 tumors initially interpreted as MT showed shared genetic aberrations in the different neoplastic components, supporting the pathologic diagnosis. NGS results for the lesion diagnosed as esophageal adenocarcinoma metastatic to lung adenocarcinoma did not support the histopathologic interpretation and were deemed inconclusive. However, the identification of an identical CDKN2A mutation in all components and in the adjacent benign lung parenchyma suggests a possible germline aberration. Sequencing results in the last case were clearly supportive of TTM. This study illustrates the role of NGS in the diagnostic workup of CNs, as an adjunct to light microscopy and immunohistochemistry.
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Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Complexas Mistas/genética , Idoso , Biomarcadores Tumorais/análise , Chicago , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/patologia , Fenótipo , Valor Preditivo dos TestesRESUMO
Hispanic and non-Hispanic black breast cancer patients are more likely than non-Hispanic white patients to be diagnosed with breast cancer that is negative for estrogen and progesterone receptors (ER/PR-negative). This disparity might be transmitted through socioeconomic and reproductive factors. Data on 746 recently diagnosed breast cancer patients (300 non-Hispanic white, 303 non-Hispanic black, 143 Hispanic) were obtained from the population-based Breast Cancer Care in Chicago Study (Chicago, Illinois, 2005-2008). Income, educational level, and census tract measures of concentrated disadvantage and affluence were combined into a single measure of socioeconomic position (SEP). Parity and age at first birth were combined into a single measure of reproductive factors (RPF). We constructed path models to estimate direct and indirect associations of SEP and RPF, and we estimated average marginal controlled direct associations. Compared with non-Hispanic white patients, non-Hispanic black patients and Hispanic patients were more likely to have ER/PR-negative disease (28% and 20% for non-Hispanic black patients and Hispanic patients, respectively, vs. 12% for non-Hispanic white patients; P ≤ 0.001). The ethnic disparity in ER/PR-negative breast cancer (prevalence difference = 0.13, 95% confidence interval: 0.07, 0.18) was reduced by approximately 60% (prevalence difference = 0.05, 95% confidence interval: -0.04, 0.13) after control for SEP and RPF. At least part of the ethnic disparity in the aggressiveness of breast tumors might be transmitted through social influences on tumor biology.
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Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Idoso , Índice de Massa Corporal , Neoplasias da Mama/etnologia , Chicago/epidemiologia , Anticoncepcionais Orais Hormonais/administração & dosagem , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Feminino , Disparidades nos Níveis de Saúde , Hispânico ou Latino/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , História Reprodutiva , Fatores Socioeconômicos , População Branca/estatística & dados numéricosRESUMO
Breast cancer risk increases transiently in the period following pregnancy; pregnancy-associated breast cancers (PABC) are more aggressive than cases diagnosed in nulliparous women. We have previously reported that in the normal human breast pregnancy results in the upregulation of a number of inflammation related genes, suggesting a pro-tumorigenic environment as well as downregulation of ESR1 (ERα) and ERBB2 (HER2) and upregulation of ESR2 (ERß), suggesting a protective effect. In this study, we aimed to investigate the possibility of differential regulation of the same gene set modulated in the normal breast, in human breast tumors following pregnancy. Gene expression was measured by real-time PCR on tumor regions isolated by laser capture microdissection from paraffin sections. Immunohistochemistry was performed on tissue microarrays (TMA) for protein expression. Hierarchical clustering was performed using the average linkage method to determine coordinate expression of sets of genes. We find that breast cancers detected within 10 years following pregnancy display a different gene expression pattern than those detected in nulliparous breast cancer patients. The gene expression difference is mainly attributable to a triple negative (TNBC) subgroup found to be more frequent in PABCs up to 10 years following a pregnancy. We also show that protein and mRNA expression levels correlate in half of the proteins tested by TMA. Despite the fact that this is a small study of 53 patients, we identified a gene expression signature that is differentially expressed in pregnancy-associated TNBC.
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BACKGROUND: Breast cancer formation is associated with frequent changes in DNA methylation but the extent of very early alterations in DNA methylation and the biological significance of cancer-associated epigenetic changes need further elucidation. METHODS: Pyrosequencing was done on bisulfite-treated DNA from formalin-fixed, paraffin-embedded sections containing invasive tumor and paired samples of histologically normal tissue adjacent to the cancers as well as control reduction mammoplasty samples from unaffected women. The DNA regions studied were promoters (BRCA1, CD44, ESR1, GSTM2, GSTP1, MAGEA1, MSI1, NFE2L3, RASSF1A, RUNX3, SIX3 and TFF1), far-upstream regions (EN1, PAX3, PITX2, and SGK1), introns (APC, EGFR, LHX2, RFX1 and SOX9) and the LINE-1 and satellite 2 DNA repeats. These choices were based upon previous literature or publicly available DNA methylome profiles. The percent methylation was averaged across neighboring CpG sites. RESULTS: Most of the assayed gene regions displayed hypermethylation in cancer vs. adjacent tissue but the TFF1 and MAGEA1 regions were significantly hypomethylated (p ≤0.001). Importantly, six of the 16 regions examined in a large collection of patients (105 - 129) and in 15-18 reduction mammoplasty samples were already aberrantly methylated in adjacent, histologically normal tissue vs. non-cancerous mammoplasty samples (p ≤0.01). In addition, examination of transcriptome and DNA methylation databases indicated that methylation at three non-promoter regions (far-upstream EN1 and PITX2 and intronic LHX2) was associated with higher gene expression, unlike the inverse associations between cancer DNA hypermethylation and cancer-altered gene expression usually reported. These three non-promoter regions also exhibited normal tissue-specific hypermethylation positively associated with differentiation-related gene expression (in muscle progenitor cells vs. many other types of normal cells). The importance of considering the exact DNA region analyzed and the gene structure was further illustrated by bioinformatic analysis of an alternative promoter/intron gene region for APC. CONCLUSIONS: We confirmed the frequent DNA methylation changes in invasive breast cancer at a variety of genome locations and found evidence for an extensive field effect in breast cancer. In addition, we illustrate the power of combining publicly available whole-genome databases with a candidate gene approach to study cancer epigenetics.
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Neoplasias da Mama/genética , Metilação de DNA , DNA Intergênico , Epigênese Genética , Regiões Promotoras Genéticas , Adulto , Idoso , Neoplasias da Mama/metabolismo , Biologia Computacional/métodos , Ilhas de CpG , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Pessoa de Meia-Idade , Análise de Sequência de DNARESUMO
Protein Tyrosine kinase 6 (PTK6/BRK) is overexpressed in the majority of human breast tumors and breast tumor cell lines. It is also expressed in normal epithelial linings of the gastrointestinal tract, skin, and prostate. To date, expression of PTK6 has not been extensively examined in the normal human mammary gland. We detected PTK6 mRNA and protein expression in the immortalized normal MCF-10A human mammary gland epithelial cell line, and examined PTK6 expression and activation in a normal human breast tissue microarray, as well as in human breast tumors. Phosphorylation of tyrosine residue 342 in the PTK6 activation loop corresponds with its activation. Similar to findings in the prostate, we detect nuclear and cytoplasmic PTK6 in normal mammary gland epithelial cells, but no phosphorylation of tyrosine residue 342. However, in human breast tumors, striking PTK6 expression and phosphorylation of tyrosine 342 is observed at the plasma membrane. PTK6 is expressed in the normal human mammary gland, but does not appear to be active and may have kinase-independent functions that are distinct from its cancer promoting activities at the membrane. Understanding consequences of PTK6 activation at the plasma membrane may have implications for developing novel targeted therapies against this kinase.
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Neoplasias da Mama/enzimologia , Glândulas Mamárias Humanas/enzimologia , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinases/metabolismo , Adolescente , Adulto , Animais , Membrana Celular/enzimologia , Feminino , Células HEK293 , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas Tirosina Quinases/genética , Transdução de Sinais , Adulto JovemAssuntos
Neoplasias da Mama/patologia , Carcinomatose Meníngea/secundário , Neoplasias da Coluna Vertebral/secundário , Antineoplásicos/uso terapêutico , Doença Crônica , Feminino , Humanos , Hipestesia/etiologia , Imuno-Histoquímica , Letrozol , Imageamento por Ressonância Magnética , Carcinomatose Meníngea/tratamento farmacológico , Carcinomatose Meníngea/patologia , Pessoa de Meia-Idade , Condução Nervosa , Nitrilas/uso terapêutico , Neoplasias da Coluna Vertebral/patologia , Sobrevida , Triazóis/uso terapêuticoRESUMO
The 14-3-3ζ gene, on 8q22, is often amplified in breast cancer and encodes a survival factor that interacts with and stabilizes many key signaling proteins. We examined the relationship between the expression of 14-3-3ζ, estrogen receptor α (ERα), and other parameters ( tumor size, grade, nodal status, progesterone receptor, HER2, EGFR, and p53) in matched primary and recurrence tumor tissue and how these factors impact time to recurrence, properties of the recurred tumors, and site of metastasis. In this cohort of over 100 patients, median time to recurrence was 3 years (range 1-17 years). Our analyses of primary tumor microarray cores revealed that 14-3-3ζ status was significantly correlated with tumor grade, size, and ERα. Women with 14-3-3ζ-positive and ERα-negative tumors had the earliest time to recurrence (median 1 yr, p < 0.001, hazard ratio 2.89), while median time to recurrence was 7 years for 14-3-3ζ-negative and ER-positive tumors. Of recurred tumors, 70-75 % were positive for 14-3-3ζ, up from the 45 % positivity of primary tumors. High expression of 14-3-3ζ also correlated with site of recurrence and showed a propensity for distant metastases to lung and chest wall. Multifactor correlation regression analysis revealed 14-3-3ζ to be a non-redundant, independent variable that adds clinical strength in predicting risk for early recurrence in ER-positive and -negative breast cancers, providing information beyond that of all other clinical pathological features examined. Thus, high expression of 14-3-3ζ in the primary tumor was significantly associated with earlier time to recurrence and with distant metastasis. Furthermore, even when the primary breast cancers were negative-low for 14-3-3ζ, the majority acquired increased expression in the recurrence. The findings underscore the detrimental role played by 14-3-3ζ in tumor aggressiveness and suggest that reducing its expression or interfering with its actions might substantially improve the clinical outcome for breast cancer patients.
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Proteínas 14-3-3/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Análise por Conglomerados , Feminino , Humanos , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , RecidivaRESUMO
Tumor surgical resection margin status is important for any malignant lesion. When this occurs in conjunction with efforts to preserve or conserve the afflicted organ, these margins become extremely important. With the demonstration of no difference in overall survival between mastectomy versus lumpectomy and radiation for breast carcinoma, there is a definite trend toward smaller resections combined with radiation, constituting "breast-conserving therapy." Tumor-free margins are therefore key to the success of this treatment protocol. We discuss the various aspects of margin status in this setting, from a pathology perspective, incorporating the past and current practices with a brief glimpse of emerging future techniques.
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The following on histology and immunohistology of Barrett's esophagus (BE) includes commentaries on the various difficulties remaining in reaching a consensus on the definition of BE; the difficulties in the characterization of intestinal and cardiac mucosa, and in the role of submucosal glands in the development of BE; the importance of a new monoclonal antibody to recognize esophageal intestinal mucosa; the importance of pseudo goblet cells; the best techniques for the endoscopic detection of Barrett's epithelium; and the biomarkers for identification of patients predisposed to the development of BE.
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Esôfago de Barrett/patologia , Anticorpos Monoclonais/imunologia , Esôfago de Barrett/imunologia , Biomarcadores/metabolismo , Biópsia , Humanos , Mucosa/patologia , Coloração e RotulagemRESUMO
The following on prevalence and incidence of adenocarcinomas in Barrett's esphophagus (BE) includes commentaries on the mechanisms of a potential protective effect of proton pump inhibitors (PPIs) on progression of BE to high-grade dysplasia; evaluation of the role of PPIs in decreasing the risk of degeneration; the geographical variations of incidence of BE; the role of the nonmorphologic biomarkers; the relationship between length of BE and development of cancer; the confounding factors in incidence rates of BE; the role of the increase of cell differentiation and apoptosis induced by PPIs in the diminution of cancer risk; the frequency of occult neoplastic foci and unsuspected invasive cancer in surgical specimens; the influence on the indications of endoscopic therapy; the overestimation of regression in surgical series; attempts to evaluate the reasons for variations of cancer incidence in the literature; and progress in screening and surveillance for BE.
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Adenocarcinoma/epidemiologia , Esôfago de Barrett/epidemiologia , Neoplasias Esofágicas/epidemiologia , Progressão da Doença , Humanos , Incidência , Prevalência , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and whether such changes are transient or persistent. We examined the expression of a customized gene set in normal breast tissue from nulliparous, recently pregnant (0-2 years since pregnancy), and distantly pregnant (5-10 years since pregnancy) age-matched premenopausal women. This gene set included breast cancer biomarkers and genes related to immune/inflammation, extracellular matrix remodeling, angiogenesis, and hormone signaling. Laser capture microdissection and RNA extraction were done from formalin-fixed paraffin-embedded reduction mammoplasty and benign biopsy specimens and analyzed using real-time PCR arrays containing 59 pathway-specific and 5 housekeeping genes. We report 14 of 64 (22%) of the selected gene set to be differentially regulated (at P < 0.05 level) in nulliparous versus parous breast tissues. Based on gene set analysis, inflammation-associated genes were significantly upregulated as a group in both parous groups compared with nulliparous women (P = 0.03). Moreover, parous subjects had significantly reduced expression of estrogen receptor alpha (ERalpha, ESR1), progesterone receptor (PGR), and ERBB2 (Her2/neu) and 2-fold higher estrogen receptor-beta (ESR2) expression compared with nulliparous subjects. These initial data, among the first on gene expression in samples of normal human breast, provide intriguing clues about the mechanisms behind the time-dependent effects of pregnancy on breast cancer risk.
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Biomarcadores/metabolismo , Mama/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Gravidez , Adulto JovemAssuntos
Neoplasias da Mama/genética , Recidiva Local de Neoplasia/genética , Receptor ErbB-2/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Recidiva , Estudos RetrospectivosRESUMO
We present a 14-month-old female child who developed multiple erythematous nodules on her abdomen 5 months after liver and small bowel transplantation. Skin biopsy revealed a dense infiltrate of large cells in the dermal and subcutaneous layers with frequent mitotic figures. The cells were noted to have abundant cytoplasm, prominent nucleoli, and open chromatin. Immunohistochemical stains were positive for CD138, CD56, Ki67 (>90%), and lambda chain restriction. Rare mature B cells (CD20) and rare T cells (CD3) were noted. She was diagnosed with high-grade post-transplant lymphoproliferative disorder most consistent with plasmablastic lymphoma.
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Gastrosquise/cirurgia , Intestino Delgado/transplante , Transplante de Fígado/efeitos adversos , Linfoma/patologia , Plasmócitos/patologia , Neoplasias Cutâneas/patologia , Linfócitos B/patologia , Biópsia , Evolução Fatal , Feminino , Humanos , Lactente , Complicações Pós-Operatórias/patologia , Pele/patologia , Volvo Gástrico/cirurgia , Linfócitos T/patologiaAssuntos
Miofibroma/diagnóstico , Neoplasias Cranianas/diagnóstico , Actinas/análise , Biomarcadores Tumorais/análise , Fasciite/diagnóstico , Fibroma Desmoplásico/diagnóstico , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/metabolismo , Fibrossarcoma/diagnóstico , Hemangiopericitoma/diagnóstico , Humanos , Hialina/metabolismo , Imuno-Histoquímica , Lactente , Masculino , Miofibroma/química , Miofibroma/cirurgia , Neoplasias Cranianas/química , Neoplasias Cranianas/cirurgia , Vimentina/análiseRESUMO
BACKGROUND: In women with duct carcinoma in-situ (DCIS) receiving breast conservation therapy (BCT), in-breast recurrences are seen in approximately 10%, but cannot be accurately predicted using clinical and histological criteria. We performed a case-control study to identify protein markers of local recurrence risk in DCIS. METHODS: Women treated for DCIS with BCT, who later developed in-breast recurrence (cases) were matched by age and year of treatment to women who remained free of recurrence (controls). RESULTS: A total of 69 women were included in the study, 31 cases and 38 controls. Immunohistochemical evaluation of DCIS tissue arrays was performed for estrogen receptor, progesterone receptor, HER-2/neu, cyclin D1, p53, p21, cycloxygenase-2 (COX-2) and peroxisome proliferator activated receptor gamma (PPARgamma). Two markers were significantly different between cases and controls on univariate analysis: strong COX-2 expression was associated with increased risk of recurrence, with 67% vs. 24% positivity in cases and controls p = 0.006; and nuclear expression of PPARgamma was associated with protection from recurrence with 4% vs. 27% positivity in cases and controls, p = 0.024. In a multivariate model which included size, grade, COX-2 and PPARgamma positivity, we found COX-2 positivity to be a strong independent risk factor for recurrence (OR 7.90, 95% CI 1.72-36.23)., whereas size and grade were of borderline significance. PPARgamma expression continued to demonstrate a protective trend, (OR 0.14, 95% CI 0.06-1.84). CONCLUSION: Our findings suggest that COX-2 and PPARgamma should be investigated further as biologic markers to predict DCIS recurrence, particularly since they are also potential therapeutic targets.
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Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/metabolismo , Ciclo-Oxigenase 2/biossíntese , Recidiva Local de Neoplasia/metabolismo , PPAR gama/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Carcinoma in Situ/enzimologia , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/enzimologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologiaRESUMO
Basal-like tumors are a newly recognized estrogen receptor (ER) negative and HER2 negative breast cancer subtype that express basal epithelial genes and are associated with poor survival. Metaplastic carcinomas are thought to belong within the basal-like group. We have recently demonstrated that the small heat shock protein alphaB-crystallin is commonly expressed in basal-like tumors and contributes to their aggressive phenotype. The current study examined the rates and patterns of alphaB-crystallin expression in whole tissue sections of human breast, including normal tissue, proliferative lesions, in situ and invasive carcinomas (ER positive, HER2 positive, basal-like, and metaplastic cancers). In normal breast tissue, proliferative lesions and in situ carcinomas, alphaB-crystallin expression was restricted to the myoepithelial cell compartment of ductal and lobular units. Most basal-like and metaplastic carcinomas demonstrated cytoplasmic expression of alphaB-crystallin (81% and 86%, respectively). Conversely, no staining for alphaB-crystallin was observed in nonbasal-like (ie, ER positive or HER2 positive) breast carcinomas. Taken together, our results indicate that alphaB-crystallin is a sensitive (81%) and specific (100%) marker for basal-like breast carcinomas. Moreover, the high rates of expression of alphaB-crystallin in metaplastic breast carcinomas (86%) suggest that these tumors may represent a histologically distinctive subset of basal-like breast tumors with a similar underlying molecular etiology.