RESUMEN
OBJECTIVE: The objective of the study was to determine the expression levels of BIK in breast cancer (BC) tissues of different histological subtype and to delve into the participation of BIK in this type of cancer. MATERIALS AND METHODS: BIK and p-BIK (the phosphorylated form) protein expressions were tested by immunohistochemistry in BC tissue microarrays (Tumoral [n = 90] and adjacent [n = 40] tissues). RESULTS: The data revealed an overexpression of BIK in invasive ductal (Grades I, IIA, and IIB) and in lobular (Grades IIA and IIB) carcinomas compared to their respective adjacent tissues. By contrast, canalicular carcinoma (Grades I and IIB) and phyllodes tumors had very low expression levels of BIK. Only levels of p-BIK were shown to be increased in invasive ductal carcinoma (Grades I, IIA, and IIB). Meanwhile, quantitative polymerase chain reaction analysis showed lower BIK levels in MCF-10A and MCF-7 cells than in MDA-MB-231 and human mammary epithelial cells. In agreement with this, BIK protein was shown to be overexpressed in MDA-MB 231 relative to MCF-7 cells. CONCLUSIONS: Our results showed an association between BIK expression and the BC tumor subtype under study, which could be related to different BIK functions in the BC subtypes.
OBJETIVO: Determinar el grado de expresión de BIK en tejidos de cáncer de mama de diferente subtipo histológico para ahondar en la participación de BIK en este tipo de cancer. MÉTODO: Por medio de inmunohistoquímica se determinó la expresión de BIK y de su forma fosforilada (p-BIK) en microarreglos de tejidos (tumores [n = 90] y tejidos adyacentes [n = 40]) y líneas celulares. RESULTADOS: Los datos mostraron una sobreexpresión de BIK en los carcinomas de tipo ductal invasivo (grados I, IIA y IIB) y lobular (grados IIA y IIB) con respecto a sus tejidos adyacentes respectivos. En contraste, el carcinoma canalicular (grados I y IIB) y los tumores filoides mostraron una baja expresión de BIK en relación con sus tejidos adyacentes respectivos. El análisis de la qPCR mostró una menor expresión de BIK en las células MCF-10A y MCF-7 en comparación con las células MDA-MB-231 y HMEC. En concordancia con esto, la expresión proteica de BIK fue mayor en las células MDA-MB 231 que en las células MCF-7. CONCLUSIÓN: Nuestros resultados mostraron una asociación entre la expresión de BIK y el subtipo tumoral en estudio, lo cual sugiere una función diferencial de BIK en el cáncer de mama.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/biosíntesis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Proteínas Mitocondriales/biosíntesis , Neoplasias de la Mama/clasificación , Carcinoma Ductal de Mama/clasificación , Carcinoma Lobular/clasificación , Femenino , Humanos , Persona de Mediana Edad , Clasificación del TumorRESUMEN
Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression of these subtypes remain poorly understood. The recent development of desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence of analytical chemistry and traditional pathology, allowing chemical profiling with minimal tissue pretreatment in frozen samples. Here, we characterized the chemical composition of molecular subtypes of breast cancer with DESI-MSI. Regions of interest were identified, including invasive breast cancer (IBC), ductal carcinoma in situ (DCIS), and adjacent benign tissue (ABT), and metabolomic profiles at 200 µm elaborated using Biomap software and the Lasso method. Top ions identified in IBC regions included polyunsaturated fatty acids, deprotonated glycerophospholipids, and sphingolipids. Highly saturated lipids, as well as antioxidant molecules [taurine (m/z 124.0068), uric acid (m/z 167.0210), ascorbic acid (m/z 175.0241), and glutathione (m/z 306.0765)], were able to distinguish IBC from ABT. Moreover, luminal B and triple-negative subtypes showed more complex lipid profiles compared with luminal A and HER2 subtypes. DCIS and IBC were distinguished on the basis of cell signaling and apoptosis-related ions [fatty acids (341.2100 and 382.3736 m/z) and glycerophospholipids (PE (P-16:0/22:6, m/z 746.5099, and PS (38:3), m/z 812.5440)]. In summary, DESI-MSI identified distinct lipid composition between DCIS and IBC and across molecular subtypes of breast cancer, with potential implications for breast cancer pathogenesis. SIGNIFICANCE: These findings present the first in situ metabolomic findings of the four molecular subtypes of breast cancer, DCIS, and normal tissue, and add to the understanding of their pathogenesis.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Lípidos/análisis , Lesiones Precancerosas/patología , Biomarcadores de Tumor/metabolismo , Mama/patología , Neoplasias de la Mama/clasificación , Carcinoma Ductal de Mama/clasificación , Carcinoma Intraductal no Infiltrante/clasificación , Progresión de la Enfermedad , Femenino , Humanos , Metabolismo de los Lípidos , Lipidómica/métodos , Lesiones Precancerosas/clasificación , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
Abstract Objective The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs). Methods We have constructed a tissuemicroarray (TMA) from87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression. Results We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph nodemetastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01). Conclusion Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.
Resumo Objetivo O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama. Métodos Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23). Resultados Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença demetástase linfonodal foimenor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2; p = 0,01). Conclusão Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.
Asunto(s)
Humanos , Femenino , Vimentina/biosíntesis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cadherinas/biosíntesis , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Queratina-5/biosíntesis , Vimentina/análisis , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/química , Inmunohistoquímica , Cadherinas/análisis , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/química , Queratina-5/análisis , Persona de Mediana EdadRESUMEN
OBJECTIVE: The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs). METHODS: We have constructed a tissue microarray (TMA) from 87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression. RESULTS: We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph node metastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01). CONCLUSION: Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.
OBJETIVO: O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama. MéTODOS: Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23). RESULTADOS: Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença de metástase linfonodal foi menor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2 ; p = 0,01). CONCLUSãO: Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.
Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cadherinas/biosíntesis , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Queratina-5/biosíntesis , Vimentina/biosíntesis , Neoplasias de la Mama/química , Neoplasias de la Mama/clasificación , Cadherinas/análisis , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/clasificación , Femenino , Humanos , Inmunohistoquímica , Queratina-5/análisis , Persona de Mediana Edad , Vimentina/análisisRESUMEN
BACKGROUND: The distinction between lobular neoplasia of the breast and ductal carcinoma in situ has important therapeutic implications. In some cases, it is very difficult to determine whether the morphology of the lesion is ductal or lobular. The aim of this study was to evaluate the value of E-cadherin and ß-catenin expression through the immunophenotypical characterization of carcinoma in situ with mixed pattern (CISM). METHODS: A total of 25 cases of CISM were analyzed considering cytology/mixed architecture (ductal and lobular), nuclear pleomorphism, loss of cell cohesion, and presence of comedonecrosis. The immunophenotype pattern was considered E-cadherin positive and ß-catenin positive, or negative. RESULTS: Nineteen (76%) cases presented a mixed cytology and / or architectural pattern, two (8%) presented nuclear pleomorphism, two (8%) presented mixed cytology and nuclear pleomorphism, and two (8%) presented comedonecrosis and nuclear pleomorphism. A complete positivity for E-cadherin and ß-catenin was observed in 11 cases (44%). In one case, the lesion was negative for both markers and showed nuclear pleomorphis. Thirteen lesions showed negative staining in areas of lobular cytology and positive staining in cells presenting the ductal pattern. CONCLUSIONS: The expression of E-cadherin and ß-catenin, combined with cytological and architectural analysis, may highlight different immunophenotypes and improve classification of CISM. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/ 1693384202970681
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Cadherinas/análisis , Carcinoma in Situ/química , Carcinoma Ductal de Mama/química , Carcinoma Lobular/química , Inmunohistoquímica , Neoplasias Complejas y Mixtas , beta Catenina/análisis , Adulto , Antígenos CD , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Carcinoma in Situ/clasificación , Carcinoma in Situ/patología , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/clasificación , Carcinoma Lobular/patología , Femenino , Humanos , Inmunofenotipificación , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and "not classified". RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and "not classified" (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and "not classified" (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa=0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype.
Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/clasificación , Carcinoma Intraductal no Infiltrante/patología , Receptores ErbB/metabolismo , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Queratina-5/metabolismo , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and “not classified”. RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and “not classified” (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and “not classified” (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa=0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype. .
Asunto(s)
Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/clasificación , Carcinoma Intraductal no Infiltrante/patología , Inmunohistoquímica , Inmunofenotipificación , /metabolismo , Receptores ErbB/metabolismo , /metabolismo , Receptores de Estrógenos/metabolismo , Biomarcadores de Tumor/metabolismoRESUMEN
Determinar si el índice de proliferación basado en la expresión del antígeno Ki-67 es un factor pronóstico que permite sub-clasificar las clases moleculares de carcinoma de mama. 312 tumores de pacientes del Instituto de Oncología Dr. Miguel Pérez Carreño con carcinoma ductal infiltrante diagnosticadas entre 2000 a 2008. Se determinó la clasificación molecular según el perfil de expresión inmunohistoquímico de receptores hormonales y HER2; el índice de Ki-67 se estratificó en bajo (≤14,50%), intermedio (14,51% -25,50%) alto (≥25,51%). Asimismo, se registró edad, grado histológico, estadio clínico y evolución de acuerdo a la supervivencia global e intervalo libre de enfermedad a través de curvas de Kaplan Meier. En la serie, se clasificaron 132 casos (42,31%) como luminal A, 66 (21,15%) como luminal B, 27 (8,65%) como HER2 y 87 (27,88%) como triple negativo. Se observó que existe variación de evolución en cada clase molecular según el índice Ki-67, y se demostró dentro de cada clase que las pacientes con índice alto presentaron menor supervivencia global e intervalo libre de enfermedad, mientras que aquéllas pacientes con índice bajo mostraron mejor pronóstico con mayor supervivencia global e intervalo libre de enfermedad P≤0,05). El índice de Ki-67 permite establecer dentro de cada clase molecular subgrupos de mejor o peor pronóstico, con valores de corte de 14,5% para los luminal A y de 25,51 para los luminal B, HER2 y triple negativo
To determine if the proliferation index based on the Ki-67 antigens expression is a prognostic factor in the molecular classes of the breast carcinoma. The study was carried on 312 tumors of patients view in the Dr. Miguel Pérez Carreño Oncology Institute with have infiltrating ductal carcinoma of the breast diagnosed between the years 2000 and 2008. The molecular classification was done according to hormonal receptor expression profile by the immunohistochemistry; the Ki-67 index was stratified into low (≤14.50%), intermediate (14.51% - 25.50%) and high (≥25.51%). Likewise the age, the histological grade, the clinical stage, and the evolution by the overall survival and the relapse free-survival through the curve of Kaplan Meier were established. In this group, 132 cases (42.31%) were classified into luminal A, 66 (21.15%) as luminal B, 27 (8.65%) as HER2 and 87 (27.88%) as triple negative. Variation in the evolution was observed in each molecular class according to the Ki-67 index. Therefore it was demonstrated in each class, that patients with high index presented lower overall survival and relapse free survival, whereas those whom had low index exhibited better prognosis with higher overall survival and relapse free survival. The proliferation index of Ki-67 expression allows to establish in each molecular class subgroups with better or worse prognosis, with cut-off values of 14.5 % for luminal A cases and 25.51 for luminal B, HER2 and triple negative
Asunto(s)
Femenino , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/diagnóstico , Inmunohistoquímica/métodos , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/diagnóstico , Modelos MolecularesRESUMEN
OBJETIVOS: fazer avaliação crítica do diagnóstico histopatológico do carcinoma ductal in situ (CDIS) da mama empregando a variação interobservador quanto ao diagnóstico, padrão arquitetural predominante, grau nuclear e grau histológico. MÉTODOS: oitenta e cinco casos com diagnóstico inicial de CDIS foram revisados por um mesmo patologista, especialista em patologia mamária, que selecionou 15 casos para análise interobservador. A análise foi realizada por cinco patologistas e um especialista internacional em patologia mamária, que receberam as mesmas lâminas e um protocolo para classificar as lesões em hiperplasia ductal atípica (HDA), CDIS e CDIS com microinvasão (CDIS-MIC). Caso o diagnóstico fosse de CDIS, os patologistas deveriam também classificá-lo quanto ao padrão arquitetural, grau nuclear e grau histológico. Os resultados foram analisados usando-se concordância percentual e o teste kappa. RESULTADOS: houve grande variação diagnóstica interobservador. Em um caso tivemos todos os diagnósticos, desde HDA, CDIS até CDIS-MIC. Usando o teste kappa para a comparação entre os diagnósticos dos cinco observadores e o especialista internacional obtivemos concordância interobservador mínima (<0,40). Quanto à classificação do CDIS em relação ao padrão arquitetural e ao grau histológico, os valores do teste kappa foram considerados ruins quanto à concordância interobservador. Os melhores resultados foram obtidos na análise da concordância quanto ao grau nuclear, com índices kappa de até 0,80, considerados como boa concordância. CONCLUSAO: os baixos índices de concordância interobservador no diagnóstico e classificação do CDIS da mama indicam a dificuldade na utilização dos critérios diagnósticos mais empregados na literatura na interpretação destas lesões e a necessidade de treinamento especifico dos patologistas não-especialistas no diagnóstico destas lesões
Asunto(s)
Humanos , Femenino , Neoplasias de la Mama , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/fisiopatología , Hiperplasia , Técnicas Histológicas/métodosRESUMEN
Realizou-se estudo retrospectivo de 90 casos de carcinoma invasivo de ductos mamários, diagnosticados por punção aspirativa por agulha fina (PAAF), com confirmação histológica, para avaliar a concordância citoistológica do grau nuclear e a reprodutibilidade intra e interobservador entre patologistas de um laboratório privado. Os preparados citológicos corados pela hematoxicilina-eosina foram examinados por dois patologistas, utilizando-se a graduação nuclear de Black modificada por Fisher (BM) e Black simplificada por Cajulis (BS). Os resultados foram controlados entre si e com a graduação de Bloom e Richardson na histologia. O índice de concordância com o grau histológico variou de 64,4% e 68,8% na classificação BM e de 86,6% a 88,8% na classificação BS. O sistema BM mostrou reprodutibilidade intra-observador de 68,8% e interobservador de 56,6% a 68,8%; enquanto o BS, de 93,3% e de 82,2% a 84,4%, respectivamente. Constatou-se que a graduação nuclear na PAAF utilizando-se o sistema de Black simplificado teve maior concordância com grau histológico e melhor reprodutibilidade intra e interobservador, quando comparada com o sistema Black modificado. Diante dos resultados demonstrados pela análise estatística (medida de concordância kappa), concluiu-se que grau nuclear é aplicável em material citológico e tem alta reprodutibilidade.
A retrospective study was performed on 90 cases of invasive breast ductal carcinoma, diagnosed by fine-needle aspiration biopsy (FNAB) and confirmed by histology, to evaluate the cyto-histological agreement of nuclear grading and to evaluate the intra- and inter-observer reproducibility between private laboratory's pathologists. Cytological smears stained with hematoxilin-eosin were graded by two independent pathologists, using Black's nuclear grading modified by Fisher (BM) and Black's simplified by Cajulis (BS). This was then compared with Bloom & Richardson's histological grade. The histological agreement rate was between 64.4% and 68.8% for BM classification and between 86.6% and 88.8% for BS. Grading using BM classification showed intra- and inter-observer reproducibility rates of 68.8% and from 56.6% to 68.8% respectively, while BS showed 93.3% and from 82.2% to 84.4% respectively. Nuclear grading in FNAB using Black's simplified system gave a higher level of agreement with the histological grade and better intra- and inter-observer reproducibility than Black's modified system. From statistical analysis (Kappa concordance level) we concluded that nuclear grade is applicable in cytological material and it shows good reproducibility.