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CONTEXT.: Definitive diagnosis of metastatic triple-negative breast carcinoma (TNBC) is challenging on cytologic samples. Recent studies demonstrated that trichorhinophalangeal syndrome type 1 (TRPS1) is a highly sensitive and specific marker for diagnosing breast carcinomas, including TNBC, on surgical specimens. OBJECTIVE.: To evaluate TRPS1 expression in TNBCs on cytologic samples and a large series of nonbreast tumors on tissue microarray sections. DESIGN.: Immunohistochemical (IHC) analysis of TRPS1 and GATA-binding protein 3 (GATA3) was performed on 35 TNBC cases on surgical specimens, and 29 consecutive TNBC cases on cytologic specimens. IHC analysis of TRPS1 expression was also performed on 1079 nonbreast tumors on tissue microarray sections. RESULTS.: Of the surgical specimens, 35 of 35 TNBC cases (100%) were positive for TRPS1, all with diffuse positivity, whereas 27 of 35 (77%) were positive for GATA3, with diffuse positivity in 7 cases (26%). Of the cytologic samples, 27 of 29 TNBC cases (93%) were positive for TRPS1, with diffuse positivity in 20 cases (74%), whereas 12 of 29 (41%) were positive for GATA3, with diffuse positivity in 2 cases (17%). Of the nonbreast malignant tumors, TRPS1 expression was seen in 9.4% (3 of 32) of melanomas, 10.7% (3 of 28) of small cell carcinomas of the bladder, and 9.7% (4 of 41) of ovarian serous carcinomas. CONCLUSIONS.: Our data confirm that TRPS1 is a highly sensitive and specific marker for diagnosing TNBC cases on surgical specimens as reported in the literature. In addition, these data demonstrate that TRPS1 is a much more sensitive marker than GATA3 in detecting metastatic TNBC cases on cytologic samples. Therefore, inclusion of TRPS1 in the diagnostic IHC panel is recommended when a metastatic TNBC is suspected.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologia , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Neoplasias da Mama/patologia , Bexiga Urinária/metabolismo , Fator de Transcrição GATA3/análise , Proteínas RepressorasRESUMO
This article reviews three informatics tools developed as part of an overall quality program in an anatomic pathology laboratory. These tools include a tracking monitor for analyzing the entire testing process through pre-analytic, analytic, and postanalytic phases; the use of digital imaging in quality control of immunohistochemistry in the analytic phase; and a results-reporting monitor for flow of postanalytic data to patient data repositories.
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Aplicações da Informática Médica , Patologia Clínica/organização & administração , Patologia Clínica/normas , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Controle de Qualidade , HumanosRESUMO
Follicular lymphoma is classified into grades (G)1, 2, and 3 based on the number of centroblasts in neoplastic follicles. However, the accuracy of manually counting these centroblasts is limited by certain cells (large centrocytes, follicular dendritic cells, and histiocytes) that could mimic centroblast morphology. The reproducibility of follicular lymphoma grading is dependent upon observer experience; therefore, significant variations occur. This study is to explore a more objective, reliable way of grading follicular lymphoma using a quantitative imaging system in conjunction with immunostains with antibodies to proliferation markers MIB-1 and S-phase kinase-associated protein 2 (SKP2). Fifty-eight follicular lymphomas (G1, n = 23; G2, n = 18; and G3, n = 17) were studied on formalin-fixed, paraffin-embedded sections. Positive nuclear staining of both Ki-67 and SKP2 was recorded using the quantitative Clarient ACIS II system (Aliso Viejo, CA, USA). Ten high-power fields (x400) from randomly selected neoplastic follicles were counted by a pathologist blinded to the previously assigned morphologic grade. The results show that the percentages of Ki-67+ and SKP2+ cells significantly differ among the different grades of follicular lymphoma. A higher grade of follicular lymphoma is associated with a higher percentage of Ki-67+ and SKP2+ cells. The overall SKP2+% cells are substantially lower than Ki-67+% cells in the same grade of follicular lymphoma. Statistical significance is observed in Ki-67+ cells between follicular lymphoma G1 and follicular lymphoma G3 and between G1 and G2. In contrast, statistical significance is noted in SKP2+% cells between follicular lymphoma G1 and follicular lymphoma G3 and between follicular lymphoma G2 and follicular lymphoma G3. The findings suggest that the SKP2 expression has better discrimination with grades of follicular lymphoma than Ki-67 expression. Compared with traditional methods, quantitation of SKP2 expression using a quantitative image analysis system might be a useful and objective approach in grading follicular lymphoma.
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Processamento de Imagem Assistida por Computador , Antígeno Ki-67/metabolismo , Linfoma Folicular/classificação , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Proteínas Quinases Associadas a Fase S/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico por Imagem , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
Morphoproteomic analysis reveals the constitutive activation of the mTOR, ERK, and NF-kappaB pathways in high risk neuroblastoma (HRN) cases as evidenced by (a) collective commonalities of: phosphorylated (p)-mTOR, p70S6K, ERK 1/2, and NF-kappaBp65 protein analytes using phosphospecific probes directed against sites of activation; (b) nuclear translocation of p-p70S6K, p-ERK 1/2, and p-NF-kappaBp65; and (c) correlative expression of the S phase-associated kinase Skp-2 (at a relatively high percentage in tumoral nuclei) and of the anti-apoptotic protein bcl-2. Based on a review of the literature, these preliminary observations appear to be the first morphoproteomic study on primary neuroblastomas.
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Neoplasias Encefálicas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Neuroblastoma/metabolismo , Proteínas Quinases/metabolismo , Proteômica , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Ciclo Celular/fisiologia , Núcleo Celular/metabolismo , Núcleo Celular/patologia , MAP Quinases Reguladas por Sinal Extracelular/análise , Humanos , Subunidade p50 de NF-kappa B/análise , Estadiamento de Neoplasias , Neuroblastoma/patologia , Proteínas Quinases/análise , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Serina-Treonina Quinases TORRESUMO
Project Santa Fe was established both to provide thought leadership and to help develop the evidence base for the valuation of clinical laboratory services in the next era of American healthcare. The participants in Project Santa Fe represent major regional health systems that can operationalize laboratory-driven innovations and test their valuation in diverse regional marketplaces in the United States. We provide recommendations from the inaugural March 2016 meeting of Project Santa Fe. Specifically, in the transition from volume-based to value-based health care, clinical laboratories are called upon to provide programmatic leadership in reducing total cost of care through optimization of time-to-diagnosis and time-to-effective therapeutics, optimization of care coordination, and programmatic support of wellness care, screening, and monitoring. This call to action is more than working with industry stakeholders on the basis of our expertise; it is providing leadership in creating the programs that accomplish these objectives. In so doing, clinical laboratories can be effectors in identifying patients at risk for escalation in care, closing gaps in care, and optimizing outcomes of health care innovation. We also hope that, through such activities, the evidence base will be created for the new value propositions of integrated laboratory networks. In the very simplest sense, this effort to create "Clinical Lab 2.0" will establish the impact of laboratory diagnostics on the full 100% spend in American healthcare, not just the 2.5% spend attributed to in vitro diagnostics. In so doing, our aim is to empower regional and local laboratories to thrive under new models of payment in the next era of American health care delivery.
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BACKGROUND: There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. METHODS: We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). RESULTS: The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis. CONCLUSIONS: A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. IMPACT: A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR.
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Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Transformação Celular Neoplásica/patologia , Neoplasias Esofágicas/patologia , Esôfago/patologia , Lesões Pré-Cancerosas , Medição de Risco , Adenocarcinoma/epidemiologia , Esôfago de Barrett/epidemiologia , Biópsia , Estudos de Casos e Controles , Progressão da Doença , Neoplasias Esofágicas/epidemiologia , Esofagoscopia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pennsylvania/epidemiologia , Prevalência , Prognóstico , Fatores de Risco , Fatores de TempoRESUMO
Blastic NK cell lymphoma is a rare hematolymphoid neoplasm. This report illustrates an unusual presentation of this entity, namely as a primary leukemia, but without skin lesions.
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Neoplasias da Medula Óssea/diagnóstico , Células Matadoras Naturais , Leucemia Linfoide/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Idoso de 80 Anos ou mais , Neoplasias da Medula Óssea/genética , Neoplasias da Medula Óssea/patologia , Antígenos CD4/análise , Antígeno CD56/análise , Humanos , Imunofenotipagem , Células Matadoras Naturais/patologia , Leucemia Linfoide/genética , Leucemia Linfoide/patologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
CCI-779 (temsirolimus), an ester of rapamycin and an inhibitor of the mammalian target of rapamycin (mTOR), is currently in phase II trials for treatment of patients with solid cancers. The mTOR functions as a checkpoint for cell proliferation, with upstream Akt and downstream p70S6K serving as its most important mediators. The aim of this study was to evaluate the expression and activation of the Akt-mTOR-p70S6K pathway in renal cell carcinoma (RCC), seeking to strengthen the rationale for targeted therapy of RCC using rapamycin or a rapamycin analogue. Tissue microarray sections containing 128 primary RCCs, 22 metastatic RCCs, and 24 non-neoplastic (normal) kidneys (NK) were immunostained with monoclonal antibodies to phosphorylated (p)-Akt (Ser473), p-mTOR (Ser2448), and p-p70S6K (Thr389). Western blotting was performed on 3 cases of clear cell RCC (CRCC) and the corresponding non-neoplastic (normal) renal tissues using the same antibodies. The immunostain scoring system included: (a) location; (b) distribution; and (c) intensity. The normal kidneys provided baseline scores for comparison. Expression of p-Akt, p-mTOR, and p-p70S6K was seen in 100% (n = 24) of NKs and nearly 100% (n = 150) of both primary and metastatic RCCs. The p-p70S6K was located in the nucleus in both NKs and RCCs. The p-Akt was observed in the nucleus and cytoplasm of NKs and in the nucleus and cytoplasm/ membrane (plasmalemma) of RCCs. The p-mTOR was identified in the membrane of NKs and the membrane/nucleus of RCCs. The levels of expression of p-p70S6K, p-mTOR, and p-Akt were significantly higher in RCC than in NK in the overall pattern (intensity and distribution, p <0.05). Western blotting also showed higher expression of p-p70S6K, p-mTOR, and p-Akt in RCCs compared to the corresponding normal kidney tissues (p <0.05). These findings indicate that correlative over-expression and activation of p-Akt, p-mTOR, and p-p70S6K are commonly observed in RCCs. After considering these findings in the context of other established protein circuitries and pathways in RCC, we propose therapeutic approaches that incorporate rapamycin-like agents and other small molecule inhibitors in a combinatorial fashion in future clinical trials for RCC.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sirolimo/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Imuno-Histoquímica , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Análise Serial de Proteínas/métodos , Proteínas Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR , Regulação para CimaRESUMO
BACKGROUND: Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. METHODS: We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. RESULTS: A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. CONCLUSION: We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. IMPACT: The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR.
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Esôfago de Barrett/diagnóstico , Biomarcadores Tumorais/análise , Progressão da Doença , Esôfago/patologia , Imunofluorescência/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adulto , Idoso , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Biópsia , Estudos de Casos e Controles , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Esôfago/metabolismo , Reações Falso-Positivas , Feminino , Humanos , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , PrognósticoRESUMO
We report the case of a 46-yr-old man with a 16-yr history of type I diabetes mellitus who developed rapid onset of nephrotic syndrome. Renal biopsy revealed diabetic nephropathy, characterized by thickened glomerular basement membranes (GBM), mild nodular glomerulosclerosis, and focal arteriolar hyalinization. Immunofluorescent (IF) studies showed strong granular IgM staining along glomerular loops, with subepithelial and intramembranous immune complex deposits along glomerular capillary loops demonstrated by electron microscopy (EM). These findings are consistent with membranous glomerulopathy with IgM as the predominant immunoglobulin. In addition, there were large aggregates of electron-dense material composed of numerous ring or spherical particles, ranging from 200 to 400 nm, in Bowman's space, which corresponded to eosinophilic aggregates on light microscopy (LM) and strong IgM stained materials by IF studies.
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Nefropatias Diabéticas/diagnóstico , Glomerulonefrite Membranosa/diagnóstico , Imunoglobulina M/imunologia , Nefropatias Diabéticas/imunologia , Glomerulonefrite Membranosa/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Determination of Her-2/neu oncogene amplification is important in the current treatment of breast carcinoma. In addition to fluorescence in situ hybridization (FISH) and immunohistochemical stain (HercepTest), chromogenic in situ hybridization (CISH) has been shown to be a sensitive and specific method to determine the Her-2/neu status of surgical specimens. The effectiveness of CISH in detecting the Her-2/neu oncogene in cytologic specimens has not been well documented. Twenty-five cases of fine needle aspirate smears and touch imprints from infiltrating ductal carcinomas were examined. Both CISH and FISH were performed on each case using a digoxigenin-labeled Her-2 DNA probe for CISH (Zymed) and both Her-2 and chromosome 17 probes for FISH (Vysis). Sixty tumor cells were evaluated in each case. The scoring system and interpretation of CISH were as follows: (1) no amplification (<5 brown dots/nucleus), (2) amplification (>10 brown dots/nucleus), and (3) low-level amplification (5-9 brown dots/nucleus). Of the 25 cases analyzed, 23 (3 amplified and 20 nonamplified) showed similar results for both methods. Two cases were discordant. In these cases, low-level amplification was suggested by CISH but nonamplification by FISH. One of the cases can be explained by polysomy for chromosome 17 by FISH. In conclusion, our preliminary data suggest that CISH is a useful technique to determine Her-2/neu oncogene status in cytologic specimens. In a case of low-level amplification, a CISH chromosome 17 probe should be used, or FISH is recommended for confirmation.
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Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Cromossomos Humanos Par 17 , Amplificação de Genes , Receptor ErbB-2/genética , Biópsia por Agulha Fina , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Hibridização In SituRESUMO
BACKGROUND: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC) methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. AIMS: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE) and the potential use as an adjunctive tool in the diagnosis of BE are described. PATIENTS AND METHODS: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22) and Barrett's with high-grade dysplasia (HGD, n = 17). Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. RESULTS: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. CONCLUSIONS: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional pathology in the assessment of BE.
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Hipertensão Maligna/diagnóstico , Hipertensão Maligna/patologia , Rim/fisiopatologia , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/patologia , Proteínas ADAM/sangue , Proteína ADAMTS13 , Adulto , Feminino , Humanos , Hipertensão Maligna/sangue , Hipertensão Maligna/enzimologia , Hipertensão Maligna/terapia , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/enzimologia , Púrpura Trombocitopênica Trombótica/terapia , Resultado do TratamentoRESUMO
The aim of this study was to elucidate protein circuitry in breast cancer based on the profiling of hormone-receptor-negative breast carcinomas using morphoproteomic and pharmacoproteomic techniques. Three human breast carcinoma cell lines (SKBR-3, MDA-175, MDA-231) were reacted by immunohistochemical (IHC) procedures to detect several categories of protein analytes. Immunoreactivities and cell compartmentalizations were scored from 0 to 3+ positivity using bright-field microscopy. An automated cellular imaging system (ACIS) was used to obtain a final combined score of staining intensity and positive cells in the IHC reactions, to enable comparisons with the visual scores and the rates of inhibition by pharmaceutical agents. FDA-approved inhibitors that target the protein circuitry were added to the cultures for 2-4 days. Proliferation assays were conducted, and in vitro inhibition rates were calculated as (control - treated)/control. Western blot analyses of whole cell lysates assessed the effects of the pharmaceutical agents on selected aspects of protein circuitry. Good to excellent correlation was observed between visual scores and ACIS scores (r values from 0.732 to 0.996 in 10 of 11 trials). Gleevec produced growth inhibition that correlated with the composite expressions of the platelet-derived growth factor (PDGF) family of ligands and receptors; captopril inhibited only MDA-175, consistent with its unique expression of plasmalemmal angiotensin-converting enzyme (ACE); and interferon (IFN)-alpha effected growth inhibition in accordance with the degree of conventional (c) protein kinase C (PKC)-alpha and phosphorylated (p)-PKCalpha/betaII expressions. Western blot analyses revealed correlative changes of several intracellular signals following incubation with these inhibitors. This study shows (a) a close association between the immunohistochemical expression of signal transduction markers and in vitro inhibition by pharmaceutical agents, and (b) correlations between the sites of action of the pharmaceutical agents and the downstream expression of proteins in hormone-receptor-negative breast cancer cell lines. Such morphoproteomic and pharmacoproteomic profiling of individual tumors may enable the pathologist and oncologist to design antitumor therapy that is customized for an individual patient.
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Neoplasias da Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Hormônio-Dependentes/metabolismo , Proteômica , Antineoplásicos/farmacologia , Benzamidas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Captopril/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Hormônios , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Interferon-alfa/farmacologia , Proteínas de Neoplasias/efeitos dos fármacos , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/patologia , Piperazinas/farmacologia , Pirimidinas/farmacologia , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/metabolismoRESUMO
CONTEXT: The increasing demand for immunohistochemistry for clinical diagnostics, in combination with an ongoing shortage of staff in the histology laboratory, has brought about a need for automation in immunohistochemistry. The current automated staining platforms vary significantly in their design and capabilities. OBJECTIVE: To review how technology has been applied to automating the process of immunohistochemical staining. DATA SOURCES: Literature review, vendor interviews, and personal practice experience. CONCLUSIONS: Each of the commercially available, automated immunohistochemistry platforms has strategic design differences that produce advantages and disadvantages. Understanding those differences can help match the demands of testing volumes, turnaround time, standardization, and labor savings to the appropriate automated instrumentation.
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Automação Laboratorial/métodos , Imuno-Histoquímica/métodos , Automação Laboratorial/normas , Humanos , Imuno-Histoquímica/normasRESUMO
OBJECTIVES: Estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin (MGB) are commonly used breast-specific immunomarkers; however, about half of metastatic breast carcinomas are negative for all three. GATA-binding protein 3 (GATA-3) has emerged recently as a sensitive and relatively specific immunomarker for breast and urothelial carcinomas, but the data documenting its expression in ER-negative breast carcinomas are limited; this often poses a dilemma in the setting of metastases. The purpose of this study is to investigate expression of GATA-3 in ER-negative breast carcinomas. METHODS: Immunohistochemical evaluation of GATA-3, GCDFP-15, and MGB on 96 ER-negative breast carcinomas was performed. RESULTS: Overall, 69% (66/96), 15% (14/96), and 35% (34/96) of ER-negative breast carcinomas expressed GATA-3, GCDFP-15, and MGB, respectively. CONCLUSIONS: Our data suggest that GATA-3 is, so far, the best breast-specific immunomarker, especially when encountering ER-negative metastatic breast carcinomas. GATA-3 should be included in the panel of immunomarkers in the workup of tumors of unknown primary.
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Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Fator de Transcrição GATA3/metabolismo , Mamoglobina A/metabolismo , Receptores de Estrogênio/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Fator de Transcrição GATA3/genética , Humanos , Imuno-Histoquímica , Proteínas de Neoplasias/metabolismo , Segunda Neoplasia Primária/metabolismoRESUMO
INTRODUCTION: Etanercept, a systemic inhibitor of α-TNF, is used for treatment of various autoimmune disorders. We report a case of spontaneous resolution of etanercept-induced lupus nephritis. CASE DESCRIPTION: A 57-year-old female patient taking etanercept for psoriasis presented with laboratory-and histology-confirmed lupus nephritis. After stopping etanercept, there was normalization of proteinuria, hematuria, serum complements, anti-dsDNA antibody, and resolution of the acute glomerular inflammatory process on repeat kidney biopsy. CONCLUSION: This case demonstrates serology- and biopsy-confirmed resolution of active lupus nephritis upon withdrawal of etanercept.
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Autoanticorpos/imunologia , Imunoglobulina G/efeitos adversos , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/patologia , Autoanticorpos/efeitos dos fármacos , Análise Química do Sangue , Creatina/sangue , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Rim/ultraestrutura , Microscopia Eletrônica , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , UrináliseRESUMO
Our recent study demonstrated the up-regulation of maspin, IMP3, and S100P and down-regulation of von Hippel-Lindau gene product (pVHL) in ductal adenocarcinoma of the pancreas. Distinction of adenocarcinoma of the gallbladder from benign/reactive glandular epithelium can be challenging if based on hematoxylin and eosin-stained sections alone. Immunohistochemical stains for pVHL, maspin, IMP3, and S100P were performed on 82 gallbladder specimens, including adenocarcinoma (n = 33) and normal/reactive gallbladder (n = 49). The results demonstrated (1) only 6.0% of adenocarcinoma cases were focally positive for pVHL, and all normal and most reactive cases (85%) were diffusely positive for pVHL; (2) maspin, IMP3, and S100P were positive in 100%, 81.8%, and 75.8% of adenocarcinoma cases, respectively; in contrast, 53.1%, 12.2%, and 30.6% of normal/reactive cases were only focally and weakly positive for maspin, IMP3, and S100P, respectively; and (3) 90.3% of adenocarcinoma cases were pVHL-negative and positive for 2 or more positive markers, whereas none of the benign/reactive cases showed this staining profile. This study demonstrates that the immunostaining profile of pVHL-/IMP3+/maspin+/S100P+ is useful in the distinction of adenocarcinoma of the gallbladder from normal/reactive conditions.
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Adenocarcinoma/diagnóstico , Proteínas de Ligação ao Cálcio/metabolismo , Colecistite/diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Proteínas de Neoplasias/metabolismo , Proteínas de Ligação a RNA/metabolismo , Serpinas/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Colecistite/metabolismo , Doença Crônica , Diagnóstico Diferencial , Neoplasias da Vesícula Biliar/metabolismo , HumanosRESUMO
Warm autoimmune hemolytic anemia (WAIHA), a rare disease (0.2-1 per 100,000 population), ranges from an indolent form with mild hemolysis to a life-threatening condition that necessitates transfusion of incompatible red cells. WAIHA can be either idiopathic or secondary to medications or to a lymphoproliferative disorder. We report a case of profound hemolytic anemia in a liver-transplant eligible patient who was diagnosed with cirrhosis secondary to non-alcoholic steatohepatitis (NASH). The patient initially was treated with red cell transfusion, iv immunoglobulin, and steroids. He developed acute renal failure that required dialysis. Subsequent management included plasmapheresis and rituximab therapy. The patient developed hepatorenal syndrome and died from progressive hepatic failure. To our knowledge, this is the first report of an association between NASH and WAIHA.