Assessment of Subgingival Biofilm and its Relationship with the Status of Tumors in a Population with Breast Cancer

This study aimed to compare the subgingival microbiota of subjects with and without breast cancer (BC). Patients with BC (Group 1; n= 50) and without BC (Group 2; n=50) with periodontitis (A) and without periodontitis (B). The study was conducted in two phases (P1 and P2). One biofilm sample was collected from each subject and analyzed by DNA-DNA Hybridization (Checkerboard DNA-DNA). The relative abundance of the subgingival microbiota differed between the Case and Control groups. However, some species were higher in patients in the Case than in Control subjects and differed between the groups in both phases. Composition of the subgingival microbial community according to the Socransky complex was related to periodontal disease, followed by clinical attachment of level (CAL ≥4mm), age, and tooth loss, which were found to be abundant in Cases when compared with controls. Patients with Tumor Grade II and III had a higher prevalence of tooth loss and CAL≥4mm. It was concluded that in individuals with BC, the sub-gingival microbiota exhibited atypical changes, but they developed periodontal disease.

El objetivo de este estudio fue comparar la microbiota subgingival de sujetos con y sin cáncer de mama (CM). Pacientes con CM (Grupo 1; n= 50) y sin CM (Grupo 2; n=50) con periodontitis (A) y sin periodontitis (B). El estudio se realizó en das fases (P1 y P2). Se recogió una muestra de biopelícula de cada sujeto y se analizó mediante hibridación ADN-ADN (tablero de ajedrez ADN-ADN). La abundancia relativa de la microbiota subgingival difirió entre los grupos de Caso y Control. Sin embargo, algunas especies fueron más altas en los pacientes del Caso que en los sujetos del Control y difirieron entre los grupos en ambas fases. La composición de la comunidad microbiana subgingival según el complejo de Socransky se relacionó con la enfermedad periodontal, seguida por el nivel de inserción clínica (CAL≥4mm), la edad y la pérdida de dientes, que se mostró abundante en los casos en comparación con los controles. Los pacientes con Tumor Grado II y III tuvieron mayor prevalencia de pérdida dental y CAL≥4mm. Se concluyó que en individuos con CM la microbiota subgingival presentó cambios atípicos, pero sin embargo, desarrollaron enfermedad periodontal.

Surgical technique and clinical effect of endoscopic assisted transaxillary breast tumor resection with the help of HUAXI Hole 3 / 中国胸心血管外科临床杂志

@#Objective    To explore the surgical technique and clinical effect of endoscopic assisted transaxillary breast tumor resection in the treatment of benign and malignant breast tumors. Methods    The clinical data of 18 patients received endoscopic breast tumor resection from September 2020 to December 2021 in the Department of Breast Surgery, West China Hospital, Sichuan University, were retrospectively analyzed to evaluate the feasibility, tumor safety and postoperative cosmetic effect. There were 7 patients with benign breast tumors (a benign breast tumor group) and 11 patients with early breast cancer (a malignant breast tumor group). Breast-Q and Scar-Q questionnaires were used to evaluate postoperative quality of life and satisfaction of patients. Results    Endoscopic breast tumor resection was performed successfully in 18 female patients, among whom 12 patients received day surgery. The mean age of benign and malignant breast tumor groups was 29.6±11.6 years and 46.7±14.3 years, the mean tumor size in pathological examination was 3.3±2.1 cm and 2.0±0.8 cm, and the operative time was 138.9±57.0 min and 177.3±46.3 min, respectively. One patient had positive resection margin and underwent intraoperative extended resection in the malignant breast tumor group. All the patients were successfully followed up, and the mean follow-up time of benign and malignant breast tumor groups was 6.8±4.0 months and 8.7±4.9 months, respectively. No complications or tumor recurrence occurred. The scores of psychosocial status, sexual well-being, chest wall status and breast satisfaction decreased one month after surgery and basically recovered to the preoperative level in one year, and the score of scar appearance increased to 64.6±5.9 points one year postoperatively. Conclusion    Endoscopic assisted transaxillary breast tumor resection can effectively improve postoperative cosmetic effect and patient satisfaction on the premise of safety.

Performance des explorations cliniques et de l'échographie mammaire dans le diagnostic des tumeurs bénignes du sein en milieu peu équipé d'Afrique subsaharienne / Performance of clinical investigations and breast ultrasound in the diagnosis of benign breast tumors in low-resource settings in sub-Saharan Africa

Contexte et objectif. Malgré leur fréquence élevée, très peu d'études ont été menées sur les tumeurs bénignes du sein (TBS) en Afrique subsaharienne. L'objectif de la présente étude a été d'évaluer la valeur diagnostique des explorations clinique et échographique mammaire des TBS en milieu peu équipé. Méthodes. Il s'agissait d'une étude documentaire, sur les TBS suivies aux Cliniques Universitaires de Kinshasa, entre janvier 2016 et décembre 2021. La valeur diagnostique des explorations clinique et échographique mammaire des TBS (sensibilité, spécificité, valeur prédictive négative VPN, VPP, coefficient Kappa) a été calculée en prenant pour référence la découverte anatomopathologique des pièces biopsiques. Résultats. Au total, 81 dossiers de TBS ont été colligés. Le Fibroadénome 58 (71,6 %), la Maladie fibrokystique (MFK) 15 (18,5 %), l'Adénome tubuleux 6(7,4 %), la Tumeur Phyllode (TP) 1(1,2 %) et le kyste 1(1,2 %) étaient les tumeurs diagnostiquées à l'anatomopathologie, après tumorectomies. A l'examen clinique, la capacité diagnostique des TBS autres que le Fibroadénome était nulle. La spécificité, la VPN et le coefficient kappa étaient respectivement, de 60,0 %, 39,1 % et 32,2 % pour le diagnostic du Fibroadénome. L'échographie mammaire était faite dans 98,6 % tandis que la mammographie seulement dans 11,1 % des cas. La majorité des tumeurs étaient classées Breast Imaging reporting and Data system (BIRADS) 2 (70,0 %). La spécificité, la VPN et le coefficient kappa étaient respectivement, de 80,6 %, 40,9 % et 39,0 % pour le Fibroadénome, et de 84,4 %, 66,7 % et 1,9 % pour la MFK. La TP était classée BIRADS3. Conclusion. L'échographie mammaire très réalisée, est très performante dans la classification BIRADS des TBS; les cliniciens exerçant en milieu peu équipé peuvent donc sans équivoque suivre les recommandations sur la prise en charge des tumeurs classées BIRADS2 et BIRADS3 à l'échographie, bien que sa performance en ce qui concerne le diagnostic différentiel de ces tumeurs soit moindre.

Diagnostic Accuracy of Prostate Specific Antigen for the Detection of Malignancy in Breast Tumors Keeping Histopathology as Gold Standard

Background/objective: Breast cancer is a major concern worldwide and causes one of the highest numbers of causalities. The general approach for the evaluation of breast cancer has become formalized as triple assessment: clinical examination, imaging (usually mammography, ultrasonography, or both), and needle biopsy. Prostatespecific antigen (PSA) has been reported to be a potential biomarker of breast cancer. The objective of the present study was to determine the diagnostic accuracy of Prostate specific antigen for the detection of malignancy in breast tumors keeping histopathology as the gold standard. Subjects and methods: This cross-sectional study was conducted at the Department of Pathology, Quaid-e-Azam Medical College, Bahawalpur Victoria Hospital Bahawalpur from April 15, 2013, to October 14, 2013. All the patients with breast lump attending Surgery Outpatient Department were included in the study. Blood samples were collected in 5 ml sterile syringes on the same day before the FNAC was done. The total prostate-specific antigen of patients was assessed by commercially available ELISA kits and values >5 ng/L were labeled as positive. Results: Total of 230 patients were included in the study. The mean age of patients was 42 years with a standard deviation of 11.681 years. About 182 patients had breast cancer on histopathology while 160 patients were positive for PSA. PSA was found to be 78.2% precise in detection, the sensitivity of 80.2%, specificity of 70.8%, and positive predictive value of 91.2% and negative predictive value of 48.5%. Conclusion: Prostate specific antigen (PSA) has significant diagnostic accuracy in breast cancer and can be used as a diagnostic and prognostic marker of breast cancer in women.

Establishment of a deep feature-based classification model for distinguishing benign and malignant breast tumors on full-filed digital mammography / 南方医科大学学报

OBJECTIVE@#To develop a deep features-based model to classify benign and malignant breast lesions on full- filed digital mammography.@*METHODS@#The data of full-filed digital mammography in both craniocaudal view and mediolateral oblique view from 106 patients with breast neoplasms were analyzed. Twenty-three handcrafted features (HCF) were extracted from the images of the breast tumors and a suitable feature set of HCF was selected using -test. The deep features (DF) were extracted from the 3 pre-trained deep learning models, namely AlexNet, VGG16 and GoogLeNet. With abundant breast tumor information from the craniocaudal view and mediolateral oblique view, we combined the two extracted features (DF and HCF) as the two-view features. A multi-classifier model was finally constructed based on the combined HCF and DF sets. The classification ability of different deep learning networks was evaluated.@*RESULTS@#Quantitative evaluation results showed that the proposed HCF+DF model outperformed HCF model, and AlexNet produced the best performances among the 3 deep learning models.@*CONCLUSIONS@#The proposed model that combines DF and HCF sets of breast tumors can effectively distinguish benign and malignant breast lesions on full-filed digital mammography.

¿Tiene valor pedir más de un perfil inmunohistoquímico en tumores multicéntricos o multifocales de mama? / Has it any value to request more than one immunohistochemical profile in multicentric or multifocal breast tumors?

Introducción La estimación de la prevalencia de tumores mamarios multicéntricos y multifocales es muy variable según los distintos estudios analizados. Esto se debe, en gran parte, a la falta de consistencia al momento de definir ambas formas de presentación. Por este motivo, muchos autores hacen referencia a este tipo de tumor como carcinoma mamario múltiple. El tnm, uicc-ajcc (7ma edición) define a esta forma de presentación como múltiples lesiones de carcinoma mamario presentes en la misma mama de manera sincrónica. Según el Colegio Americano de Patólogos (cap), la caracterización biológica de la lesión de mayor tamaño tumoral es suficiente, salvo que se presenten discordancias entre los tipos histológicos o grados tumorales. A pesar de que la estrategia de evaluar una única lesión en este aspecto tiene claras ventajas en costos y viabilidad, el cáncer de mama es considerado en sí mismo una enfermedad heterogénea, y, al seguir las recomendaciones anteriormente expresadas, se estaría asumiendo que estos tipos de tumores múltiples tienen un comportamiento biológico homogéneo. Por tal motivo, en el presente estudio se analiza el comportamiento biológico (re, rp, her2 y Ki-67) en cada foco tumoral presente, para poder establecer si, al seguir las recomendaciones vigentes actualmente, no estaríamos subtratando a un grupo de nuestras pacientes. Objetivos Evaluar la concordancia en los perfiles inmunohistoquímicos de cada tumor presente de manera sincrónica en la mama. Establecer la asociación entre los tamaños, los tipos histológicos y el grado tumoral. Material y método Se realizó un estudio observacional, retrospectivo en pacientes con diagnóstico y confirmación por estudio histopatológico de pieza quirúrgica de carcinoma mamario multifocal o multicéntrico. De un total de 722 pacientes, se obtuvieron datos de 45 historias clínicas, en un período comprendido, entre marzo de 2015 y septiembre de 2016 (18 meses). Las pacientes analizadas fueron diagnosticadas y tratadas en la Unidad de Mastología de la Clínica Breast y el Hospital Italiano de la Ciudad de La Plata, Buenos Aires, Argentina. Los resultados histopatológicos e Inmunohistoquímicos (ihq) se obtuvieron de los patólogos pertenecientes a nuestro centro mastológico. El perfil ihq se realizó en tejido tumoral obtenido mediante biopsia con aguja gruesa o pieza quirúrgica. Se determinó: Receptores Hormonales para Estrógeno (re) y Progesterona (rp), her2 y Ki-67. Resultados • Se observó una incidencia de 6,23% de tumores multicéntricos, multifocales. • En cuanto al tipo histológico, la correlación entre biopsia con aguja gruesa y análisis de pieza quirúrgica fue del 100% (n:45 pacientes). • Grado histológico tumoral en los distintos focos: 84% (n=38) de concordancia y 16% (n=7) de discordancia. • Variabilidad de subtipos tumorales en cada foco: el 67% (n=30) no presentó discordancias. • Perfil inmunohistoquímico (ihq): el porcentaje de pacientes con concordancia en el perfil inmunohistoquímico y el subtipo tumoral fue superior al grupo de pacientes que presentaron discordancias. En el grupo de pacientes con discordancias, un 20% sobreexpresó el marcador her2. Conclusiones Teniendo en cuenta la heterogeneidad tanto intratumoral como entre los distintos focos que se presenta en estos tumores múltiples, es importante obtener la mayor información posible sobre la morfología y el perfil inmunohistoquímico.

Estimates of the prevalence of multicentric and multifocal breast tumors is highly variable depending on the different studies analyzed, and this is due largely to the lack of consistency when defining both forms of presentation. For this reason, many authors refer to this type of tumor as multiple breast carcinoma. The tnm (7th edition) defines this presentation as multiple lesions of breast carcinoma present in the same breast synchronously. According to the College of American Pathologists (cap), biological characterization of the lesion of the largest tumor is sufficient, unless discrepancies between the histological tumor types or degrees are presented. Although the strategy of evaluating a single lesion in this regard, has clear advantages in cost and viability, breast cancer is considered itself an heterogeneous disease, and following the recommendations previously expressed, it would be assuming that these type of multiple tumors have a homogeneous biological behavior. Therefore, in this study the biological behavior (er, pr, her2 and Ki-67) is analyzed in each tumor focus, to determine whether to follow the recommendations currently in force, we would not be sub-treatment a group of our patients.

GATA 3, an immunohistochemical expression and clinicopathological correlation with breast tumors / 国际药学研究杂志

Background: GTAT 3 is a transcription marker for many tumors including breast tumors. Its play an important role in proliferation and differentiation of cell. Aim: The aim of the present study for assessment GATA 3 expression in Iraqi women with breast tumors and its association with histological grades and pathological stages. Materials and Methods: A retrospective study of 72 FFPET of breast tumors, 57/72 were primary breast malignant tumors (infiltrative ductal carcinoma IDC and infiltrative lobular carcinoma ILC), and 15/72 were benign breast tumors. Results: The nuclear staining of (1% or more) of tumor cells was considered positive expression for GATA 3 (cut off value 1%), 47 of 57 (82.5%) of malignant tumors were positive expression of GATA 3, while 3 of 15 (20.0%) of benign tumors were negative expression, (P 0.05). Conclusion: GATA 3 is a specific markers for breast carcinoma and its can be used for diagnosis of the malignant from benign tumors and it's considered a good prognosis marker for breast cancer.

PHYLLODES TUMORS OF THE BREAST: A RETROSPECTIVE EVALUATION OF CASES FROM THE HOSPITAL DO SERVIDOR PÚBLICO ESTADUAL DE SÃO PAULO / Tumor filoides de mama: avaliação retrospectiva de casos do Hospital do Servidor Público Estadual de São Paulo

Objective: To evaluate the clinical and pathological characteristics of phyllodes tumors, and to identify possible associated risk factors for relapses among patients from the Breast Surgery Department of the Hospital do Servidor Público Estadual of São Paulo (HSPE-SP). Methods: Retrospective, descriptive study of data from 52 patients, between 1976 and 2013. The following data were collected: age, tumor size, histological type, surgical margins, type of surgery performed, relapses and amount of time before relapse. Results: The mean age of the patients was 45.7 years old, the mean size of the tumor was 7.8 cm. A mastectomy was performed on 12 patients, and the others underwent a wide excision. Benign phyllodes tumors were found in 30 patients, and the others were found as follows: 11 with borderline tumors and 11 with malign phyllodes tumors. There was no statistical relevance with regard to the relapses and the characteristics evaluated. Conclusion: The sample studied has similar clinical and pathological characteristics as described in the scientific literature, with the mean age at diagnosis being 45 years old, the mean tumor size, 7.8 cm. The majority found were benign phyllodes tumors and 33% were from relapses. There was no statistical significance between the evaluated variables and the risk for relapse.

Objetivo: Avaliar as características clínicas e patológicas do tumor filoides e identificar fatores relacionados com risco de recidivas em pacientes acompanhadas no ambulatório de Mastologia do Hospital do Servidor Público Estadual de São Paulo (HSPE-SP). Método: Estudo retrospectivo descritivo de dados de 52 pacientes, entre 1976 e 2013, dentre os quais: idade, tamanho do tumor, tipo histológico, margens cirúrgicas, tipo de cirurgia, recidivas e tempo para recidiva. Resultados: A idade média das pacientes foi 45,7 anos. O tamanho médio do tumor foi de 7,8 cm. O tratamento em 12 pacientes foi a mastectomia, e as demais 40 a excisão ampla. O tipo histológico encontrado em 30 pacientes foi tumores benignos, 11 malignos e 11 de variedade borderline. Após o seguimento médio de 53,93 meses, observaram-se 17 recidivas. Não houve relevância estatística entre a recorrência local e as variáveis avaliadas. Conclusões: A amostra avaliada tem características clínicas e patológicas condizentes com a literatura, com média de idade de 45 anos, tamanho do tumor de 7,8 cm, sendo encontrados na maioria tumor filoides benigno e 33% de recidivas. Não houve significância estatística entre características avaliadas e o risco de recidiva.

The coronal plane of automatic breast volume scaner for modified BI?RADS classification of clinical study / 实用医学杂志

Objective To investigate the clinical value of modified BI?RADS classification by using the coronal plane of automatic breast volume scaner. Methods The total of 201 BI?RADS 3~5 classification of breast masses were retrospectively analyzed. All masses underwent conventional ultrasound and ABVS examination. Using BI? RADS classification standard terms to describe various information of breast masses, and record the coronal image of the masses on the complete interface echo, convergence sign, angle, burr, which classified BI?RADS ultimately. Results The coronal plane of convergence sign, complete interface echo, angulation and burr were significantly different between benign and malignant tumors (P<0.0001). The sensitivity of ABVS convergent sign in diagnosing breast malignant tumors was 68.2%, specificity was 93.4% and accuracy was 82%. The conventional ultrasound combined with the coronal feature of ABVS modified by BI?RADS classification showed that 3 kinds of malignant rate reduced from 8.5%to 3.2%. The rate of malignant 4a decreased from 25.2%to 12.1%and the rate of malignant 5 increased from 94.2% to 98%. Conclusion The convergence sign of ABVS can be used as a significant independent predictor of breast malignant tumors;ultrasound combined with ABVS is helpful to improve the accuracy of ultrasound BI?RADS classification.

Breast tumor classification in ultrasound images using support vector machines and neural networks

Abstract Introduction The use of tools for computer-aided diagnosis (CAD) has been proposed for detection and classification of breast cancer. Concerning breast cancer image diagnosing with ultrasound, some results found in literature show that morphological features perform better than texture features for lesions differentiation, and indicate that a reduced set of features performs better than a larger one. Methods This study evaluated the performance of support vector machines (SVM) with different kernels combinations, and neural networks with different stop criteria, for classifying breast cancer nodules. Twenty-two morphological features from the contour of 100 BUS images were used as input for classifiers and then a scalar feature selection technique with correlation was used to reduce the features dataset. Results The best results obtained for accuracy and area under ROC curve were 96.98% and 0.980, respectively, both with neural networks using the whole set of features. Conclusion The performance obtained with neural networks with the selected stop criterion was better than the ones obtained with SVM. Whilst using neural networks the results were better with all 22 features, SVM classifiers performed better with a reduced set of 6 features.

A Meta-analysis of the value of mammography,ultrasound and MRI in the diagnosis of breast tumors / 实用放射学杂志

Objective To investigate the value of mammography (MAM),ultrasound (US)and MRI in the diagnosis of breast tumors using a Meta-analysis.Methods A systematic search of relevant literatures was done from CNKI,CBM,VIP,EMBASE OvidSP,PubMed and The Cochrane Library databases.Some related literatures about MAM,US and MRI in the diagnosis of breast tumors and the quality was evaluated,and the available information was extracted.The Meta-analysis was then performed by a Meta-disc 1.4 software,and a Review Manager 5.3 software was used to calculate the summary receiver operating characteristic curves and the area under the curve.Results The diagnostic effect of the MAM+US+MRI was significantly higher than that of mammography or ultrasound (P <0.05).The MAM study heterogeneity among sources was affected by whether it based on BI-RADS diagnostic criteria,and US study heterogeneity was affected by average age of patients.However,the MRI heterogeneity between studies displayed by regression analysis was not affected by each covariate.The diagnostic sensitivity and specificity were 76% (95%CI:0.73-0.79)and 72% (95%CI:0.69-0.75)for MAM,85% (95%CI:0.82-0.87)and 70% (95%CI:0.67-0.73)for US,and 95% (95%CI:0.93-0.96)and 72% (95%CI:0.69-0.75)for MRI,respectively.And the area under curve (AUC)of summary receiver operating characteristic (SROC)curve was 82.0%,88.5% or 97.4%, respectively.Moreover,the AUC of combined three methods together was 98.3%.Conclusion The value of MAM,US and MRI in diagnosis of breast tumor is higher,and the highest one exists when the combined three methods together are used.

Reconstrução mamária com tecido autólogo: 380 casos consecutivos / Breast reconstruction with autologous tissue: 380 consecutive cases

INTRODUÇÃO: A reconstrução mamária desempenha papel importante no tratamento do câncer de mama. Várias opções estão disponíveis para a reconstrução autóloga, sendo as mais difundidas o retalho do reto abdominal (TRAM), o retalho de grande dorsal e retalho muscular local. O trabalho visa demonstrar a experiência inicial na reconstrução mamária com tecido autólogo, acrescido ou não de implante. MÉTODO: Foi realizada análise retrospectiva de prontuários de 367 pacientes que foram submetidas à reconstrução mamária imediata e tardia com retalho do reto abdominal (TRAM) unipediculado ou retalho de grande dorsal (GD) ou retalho muscular local (RL). RESULTADOS: Foram reconstruídas 380 mamas. Em 156 pacientes, a técnica foi TRAM; em 179, GD; e, em 49 pacientes, outras técnicas foram empregadas. O tamanho dos implantes variou entre 155 cc e 640 cc. A idade média das pacientes foi de 49,33 anos. 197 pacientes foram operadas do lado direito, 169 do lado esquerdo e em 14 pacientes a reconstrução foi bilateral. A reconstrução foi imediata em 80% das pacientes. Houve poucas complicações moderadas (deiscência parcial da sutura, com necessidade de ressutura) e graves (liponecrose do retalho, extrusão do implante após infecção e tromboembolismo pulmonar) e, ainda, algumas complicações menores que não demandaram correção cirúrgica. CONCLUSÕES: A reconstrução mamária com tecido autólogo fornece ao cirurgião plástico um método consistente e confiável de reconstrução mamária, com resultados estéticos muito satisfatórios e com morbidade pequena para pacientes selecionadas.

INTRODUCTION: Breast reconstruction plays an important role in the treatment of breast cancer. Several options are available for autologous breast reconstruction, the more widespread being the transverse rectus abdominis myocutaneous (TRAM) flap, the latissimus dorsi myocutaneous (LDM) flap, and the local muscle (LM) flap. The objective of this work was to demonstrate the initial experience in breast reconstruction with autologous tissue, with or without implants. METHOD: A retrospective analysis was performed of medical charts of 367 patients who underwent immediate and delayed breast reconstruction with the unipediculated TRAM flap, LD flap, or LM flap. RESULTS: Three hundred eighty breasts were reconstructed. There were 156 TRAM flap procedures, 179 LD flap procedures, and 49 other techniques. The size of the implants ranged between 155 cc and 640 cc. The mean age of the patients was 49.33 years. One hundred ninety-seven patients underwent surgery on the right side and 169 on the left; 14 patients underwent bilateral reconstruction. Reconstruction was immediate in 80% of the patients. There were few moderate (partial dehiscence of the wound requiring suturing) and severe complications (flap liponecrosis, extrusion of the implant after infection, and pulmonary thromboembolism) and some minor complications that did not require surgical correction. CONCLUSIONS: Breast reconstruction with autologous tissue provides the plastic surgeon with a consistent and reliable method of breast reconstruction, with very satisfactory aesthetic results and low morbidity in selected patients.

Investigação do papel de SIGIRR/IL-1R8 no crosstalk entre células tumorais e o infiltrado leucocitário / Investigating the role of SIGIRR/IL-1R8 in the crosstalk between tumor cells and the immune system

Células tumorais desenvolvem diversas estratégias para escapar da identificação e eliminação pelo sistema imune. Dessa forma, a investigação dos mecanismos envolvidos na comunicação celular no microambiente tumoral e na desregulação local do sistema imune é crítica para uma melhor compreensão da progressão da doença e para o desenvolvimento de alternativas terapêuticas mais eficazes. Nós aqui demonstramos que SIGIRR/IL-1R8, um importante regulador negativo de receptores de Interleucina-1 (ILRs) e receptores do tipo Toll (TLRs), apresenta expressão aumentada em uma linhagem celular epitelial mamária transformada pela superexpressão do oncogene HER2 e em tumores primários de mama, e promove o crescimento tumoral e metástase através da modulação da inflamação associada ao câncer e da atenuação da resposta imune antitumoral. Observamos que IL-1R8 tem sua expressão correlacionada com HER2 em tecidos mamários e sua alta expressão é fator de pior prognóstico em câncer de mama de baixo grau. Notavelmente, níveis aumentados de IL-1R8 foram observados especialmente nos subtipos HER2+ e Luminais de tumores de mama, e sua expressão aumentada em células epiteliais de mama transformadas por HER2 diminui a ativação da via de NF-κB e a expressão de diferentes citocinas pro-inflamatórias (IL-6, IL-8, TNF, CSF2, CSF3 e IFN-ß1). Meio condicionado de células transformadas por HER2, mas não de variantes celulares com o gene IL-1R8 silenciado, induz a polarização de macrófagos para o fenótipo M2 e inibe a ativação de células NK. Em um modelo murino transgênico de tumorigênese espontânea mediada por HER2, MMTV-neu, verificamos que a deficiência de IL-1R8 (IL-1R8-/-neu) retardou o aparecimento de tumores e reduziu a incidência, a carga tumoral e a disseminação metastática. Contudo, não foram observadas diferenças significativas no crescimento tumoral quando animais IL-1R8-/-neu receberam medula óssea de animais IL-1R8+/+, confirmando um papel importante da expressão de IL-1R8 em células não hematopoiéticas na tumorigênese da mama. Tumores IL-1R8+/+neu apresentaram maiores níveis de citocinas pró-inflamatórias como IL-1ß e VEGF, e menores níveis da citocina imunomodulatória IFN-γ. Além disso, tumores que expressavam IL-1R8 apresentaram menor infiltrado de células NK maduras, células dendríticas (DCs) e linfócitos T-CD8+ e um maior infiltrado de macrófagos M2 e linfócitos T-CD4+. Coletivamente, esses resultados indicam que a expressão de IL-1R8 em tumores de mama pode representar um novo mecanismo de escape da resposta imune e suportam IL-1R8 como potencial alvo terapêutico

Tumor cells develop numerous strategies to fine-tune inflammation and avoid detection and eradication by the immune system. Identification of new players that regulate the cellular crosstalk within the tumor microenvironment and promote local immune dysregulation is critical to understand disease progression and to improve therapeutic strategies. Here, we demonstrate that SIGIRR/IL-1R8, a negative regulator of IL-1R and TLRs, is up-regulated in a HER2-transformed epithelial mammary cell line and in primary breast tumors and promotes tumor growth and metastasis by modulating cancer-related inflammation and impairing anti-tumor immunity. IL-1R8 expression is correlated with HER2 in mammary tissue, and higher tumor IL-1R8 expression is a poor prognostic factor in lower grade breast tumors. Notably, higher levels of IL-1R8 expression were observed in HER2+ and Luminal breast tumor subtypes and IL-1R8 up-regulation in HER2-transformed mammary epithelial cells inhibited NF-κB activation and the expression of pro-inflammatory cytokines (IL-6, IL-8, TNFα, CSF2, CSF3, IFN-ß1). Conditioned medium from HER2-transformed cells, but not from IL-1R8 knockdown variants, induced M2-macrophage polarization and inhibited natural-killer (NK) cell activation. IL-1R8 deficiency in a transgenic mouse model of breast tumorigenesis (MMTV-neu) significantly delayed tumor onset and reduced tumor incidence, burden and metastasis. No significant differences in tumor growth were observed when IL-1R8-/-neu mice were transplanted with bone marrow from IL-1R8+/+ animals, confirming an important role for IL-1R8 expression in non-hematopoietic cells during breast tumorigenesis. IL-1R8+/+neu mammary tumors presented higher levels of pro-inflammatory cytokines such as IL-1ß and VEGF, but lower levels of IFN-γ. Besides, a lower infiltrate of mature NK cells, dendritic cells (DCs) and CD8+ T cells but higher infiltrate of M2-macrophages and CD4+ T cells were present in IL-1R8 expressing tumors. Collectively, our results support IL-1R8 expression as a novel tumor immune escape mechanism in breast cancer and putative target for immunotherapy

Construction and in vitro characterization of dual-modality single-photon emission computed tomography-MRI nanoprobes targeting HAb18G/CD147 in breast tumors / 中华放射学杂志

Objective To prepare dual?modality single?photon emission computed tomography (SPECT)?MRI molecular nanoprobes targeting HAb18G/CD147 expressed on breast cancer cell membranes and investigate the physicochemical and biological properties in vitro. Methods Superparamagnetic iron oxide nanoparticles (SPIOs) were prepared by one?pot reaction method as described. The single?chain antibody fragments HAb18F(ab')2 were conjugated to SPIOs via chemical method and then labeled with 125I using Iodogen method. The final 125I?SPIO?HAbF18(ab')2 nanoprobes were purified. SPIOs or 125I?HAb18F(ab')2 were used as control. We carried preliminary evaluation on their physicochemical properties and biological characteristics in vitro: transmission electron microscope (TEM) and dynamic light scattering (DLS) were used to measure these nanoparticle sizes and the hydrodynamic diameters. The MRI T2 transverse relaxation efficiency of these nanoprobes at different Fe2+concentrations were measured with 1.5 T clinical MR scanner. The 125I?SPIO?HAb18F(ab')2 and 125I?HAb18F(ab')2 radiochemical purity were measured by thin layer chromatography and the radio chemical yield was calculated. We also conducted stability tests in vitro and octanol/water partition coefficient experiments. Two breast tumor cell lines, MDA?MB?231 (HAb18G?overexpressing cells,experimental group) and MDA?MB?468 (control), were used for assessment of cells viability at different Fe2 + concentrations (1, 5, 10, 20, 40 μg/ml) by methyl thiazolyl tetrazolium assay. Specific binding experiments in vitro included two parts:magnetic resonance imaging and radionuclide tests, the above?mentioned breast cancer cell lines were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes respectively and took MDA?MB?231 cells which were not treated as blank group. First comparing the MR signal intensity differences among experimental group, the control group and blank group, then calculated the rate of MRI signal changes;Two breast tumor cell lines, MDA?MB?231 and MDA?MB?468 were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes too, then measured radioactivity counting byγcounter at different time and calculated the cell binding rates, and did statistical analysis by using one?way ANOVA. Results The SPIOs were fairly homogeneous with an average core size of (10.32±1.30) nm;the SPIO and 125I?SPIO?HAb18F(ab')2 hydrodynamic diameter of 44.80 and 52.64 nm, and MRI scanning showed that the transverse relaxation efficiency of SPIO and 125I?SPIO?HAb18F(ab')2 were 38.79 and 106.73 mM-1 · s-1, respectively. The radio chemical yield of 125I?SPIO?HAbF18(ab')2 and 125I?HAb18F(ab')2 were 41.90% and 85.50%, respectively. The radio chemical yield of the two groups were >95%, suggesting well stability in vitro. The lipo?hydro partition coefficient values were -0.99 ± 0.03 and-1.49 ± 0.08, respectively, which demonstrated that they were both water?soluble substances. Different Fe2+concentrations (1,5,10,20,40μg/ml) of 125I?SPIO?HAb18F(ab')2 on breast cancer cell lines MDA?MB?231 and MDA?MB?468 showed no significant inhibition of cell proliferation (F values were 0.78, 0.66; P values were 0.58, 0.66). The cell?specific binding experiment showed: MRI signal intensity values on experimental group, the control group and the blank group were (1 670 ± 5), (1 930 ± 8), (2 349 ± 14), respectively, significant differences existed among these groups (F=4 408.48,P=0.000), the rate of signal intensity change of experimental group and the control group were 28.87%,17.78%. SPECT:MDA?MB?231 could uptake 125I?SPIO?HAb18F(ab')2, the cell binding rates were (6.52 ± 0.60)% and (10.52 ± 2.04)% in 20 min and 4 h, respectively.Conclusions Our results suggested that the dual?modality SPECT?MRI nanoprobes 125I?SPIO?HAb18F(ab')2 were prepared successfully with good physicochemical properties and biological characteristics in vitro. These dual?modality molecular imaging nano?probes may have potential to improvearly detection and diagnosis of HAb18G/CD147?expressing cancers and to facilitate the development of HAb18G/CD147?directed interventions.

Mastopatia linfocítica simulando neoplasia de mama: relato de caso / Lymphocytic mastopathy mimicking breast malignancy: a case report

A mastopatia linfocítica acomete mulheres jovens e de meia idade e está frequentemente associada a doenças autoimunes. Seu diagnóstico é feito associando achados clínicos (espessamento ou nódulo mamário endurecido), radiológicos (aumento da densidade mamária, nódulo e calcificações), ultrassonográficos (nódulo com sombra acústica posterior), histopatológicos (fibrose e infiltrado linfocítico) e imuno-histoquímicos. É uma entidade benigna que pode simular carcinoma. Neste artigo, relata-se um caso de paciente com mastopatia linfocítica.

Lymphocytic mastopathy affects both young and middle-aged women and is frequently associated with autoimmune diseases. Diagnosis is done by associating clinical (breast tissue thickening or hardened breast lump), radiological (increased breast density, presence of mass and calcifications), sonographic (nodule with posterior acoustic shadowing), histopathological (fibrosis and lymphocytic infiltrate) and immunohistochemical findings. Lymphocytic mastopathy is a benign entity that may mimic carcinoma. The authors report the case of a patient with lymphocytic mastopathy.

Contrastive study on conventional ultrasound, compression elastography and acoustic radiation force impulse imaging in the differential diagnosis of benign and malignant breast tumors / 中南大学学报(医学版)

Objective: To evaluate the diagnostic performance of conventional ultrasound, compression elastography (CE) and acoustic radiation force impulse imaging (ARFI) in diff erential diagnosis of benign and malignant breast tumors. Methods: A total of 98 patients with liver lesions were included in the study. The images of conventional ultrasound, CE and the values of virtual touch tissue quantiifcation (VTQ) of breast lesions were obtained. hTe diagnostic performance of conventional ultrasound, CE and ARFI were assessed by using pathology as the gold standard, and then evaluate the diagnosis effciency of these three approaches in differential diagnosing benign and malignant breast tumors. Results: The specificity, sensitivity and accuracy in the diagnosis of malignant breast tumors for conventional ultrasound were 80.0%, 81.1% and 81.7%, respectively, whereas for CE elastic score were 85.7%, 86.7% and 86.3%, respectively. With a cutoff value of 3.71 for the SR, the sensitivity, speciifcity, accuracy in diagnosis of malignant breast tumors were 97.1%, 83.3% and 88.4%, respectively. With a cutoff value of 3.78 m/s for VTQ, the sensitivity, speciifcity, accuracy in diagnosis of malignant breast tumors were 94.3%, 91.7% and 92.6%, respectively. The difference in diagnosis efficiency among ARFI, CE and conventional ultrasound in differential diagnosis of benign and malignant breast tumors was signiifcant (P<0.05). Conclusion: Conventional ultrasound, CE and ARFI are all useful for the differential diagnosis of benign and malignant breast tumors. But the diagnosis effciency of ARFI is superior to CE and conventional ultrasound. The three approaches can help each other in differential diagnosis of benign and malignant breast tumors.

Emprego do cell block de agarose como método complementar no diagnóstico citológico de tumores mamários caninos / Employment of cell block of agarose as additional method in the cytological diagnosis of canine mammary tumors

Os tumores mamários são neoplasias comuns em diversas espécies, sendo os processos oncológicos de maior incidência em cães. A elevada frequência e agressividade desses processos justificam a busca de métodos diagnósticos e prognósticos rápidos, de custo reduzido e menor invasividade, visando a uma abordagem cirúrgica e terapêutica adequada. O presente estudo avaliou a adequação da utilização da técnica de cell block de agarose como método diagnóstico complementar aos esfregaços tradicionais no diagnóstico desses processos. Para tanto, foram obtidas 51 amostras citológicas de tumores mamários de 30 cadelas que passaram por excisão tumoral no HOVET-UMESP, comparando-se os resultados obtidos a partir dos esfregaços, de cell blocks, e de sua associação (esfregaços cell blocks-1) com o diagnóstico histopatológico. Os melhores resultados foram obtidos mediante a associação dos métodos, reduzindo os resultados falso-negativos e elevando a correlação cito-histológica, reforçando a importância da citologia na rotina oncológica veterinária.

The breast tumors are common neoplasms in several species, with high incidence in dogs. The high frequency and aggressiveness of these cases justifies the search for rapid, low cost and less invasive diagnostic methods, seeking for surgical approach and appropriate therapy. This study evaluated the appropriateness of the use of the agarose cell block technique as a diagnostic tool to complement traditional smears in the diagnosis of these processes. Therefore, it was obtained 51 samples from 30 dogs with breast tumors that underwent tumoral excision at the HOVET-UMESP, comparing the results obtained from smears, cell blocks, alone and in association (smears cell blocks-1), with the histopathologic diagnosis. The best results were obtained with the association of smears and cell block analysis, reducing the false negative results and increasing the cyto-histological correlation, reinforcing the importance of the use of cytology in routine veterinary oncology.

Breast Metastasis from Renal Cell Carcinoma: Rare Initial Presentation of Disease Recurrence after 5 Years / 한국유방암학회지

Metastasis to the breast from extra-mammary tumors is rare with only a few sporadic cases reported. We present a 58-year-old female patient diagnosed with renal cell carcinoma. Five years ago she had a radical nephrectomy and was free of disease, then discovered solitary breast mass following self-examination. The patient presented to the breast clinic for evaluation whereupon the breast mass was identified on physical and radiological examinations. Fine needle aspiration was diagnostic of metastatic renal cell carcinoma and subsequent imaging studies demonstrated multiple pulmonary deposits and recurrent renal mass in the tumor bed of the diseased site. In a multidisciplinary clinic, the patient was elected for excision biopsy followed by systemic tyrosine kinase inhibitor therapy. Six months later she had brain metastasis and received whole brain irradiation followed by palliative therapy. We are presenting this rare case with the aim of increasing awareness of breast secondaries.

Comparison of stromal CD10 expression in benign, borderline, and malignant phyllodes tumors among Egyptian female patients.

Background: Phyllodes tumors are group of biphasic fibroepithelial tumors of the breast of varying malignant potential, ranging from benign tumors to fully malignant sarcomas. According to the Egyptian National Cancer Institute, female malignant cases showed appreciable increase in the recent time period for breast cancer with the malignant phyllodes tumors representing 0.41% of cases in the year 2003-2004. Aims: This is an immunohistochemical study to compare CD10 expression in benign, borderline, and malignant phyllodes tumors, in order to highlight its diagnostic and prognostic values. Materials and Methods: This study conducted 34 Egyptian female cases of phyllodes tumors of different grades to be studied histologically and immunohistochemically using antibodies against CD10. Statistical Analysis: The Chi-square test was used to determine differences in CD10 expression between benign, borderline, and malignant tumors. One-way ANOVA test was used to determine whether the difference was significant. Significance was established at P<0.05. Results: In the 24 cases of benign phyllodes tumors, only four cases (16.7%) showed positive CD10 reactivity. Three cases (60%) out of five borderline phyllodes tumors showed positive CD10 reactivity, while four (80%) out of five cases of malignant phyllodes tumors showed positive CD10 staining. Conclusion: From these highly significant results, we believe that there is a strong correlation between CD10 expression and tumor grade, which could be an important observation that may have both diagnostic and prognostic implications as well as promising potential target for development of novel therapies.

Doença de Paget: a importância do especialista / Paget's disease: the importance of the specialist

Mulher, 26 anos, com história de lesão eritêmato-escamosa no mamilo esquerdo, há dois anos. Era acompanhada pelo seu ginecologista como eczema crônico em uso de corticoide tópico, sem melhora. Encaminhada ao nosso serviço, realizou-se o diagnóstico de doença de Paget mamária associada ao carcinoma intraductal. Antes da quarta década de vida, a doença de Paget é rara, e, na grande maioria dos casos, está associada ao carcinoma mamário. Essa enfermidade constitui diagnóstico diferencial obrigatório do eczema do mamilo. O diagnóstico tardio, como no caso relatado, implica em pior prognóstico e aumento da morbidade, já que terapêutica mutilante é necessária.

A twenty-six-year-old woman with a two-year history of an erythematous, scaly lesion on the left nipple was being followed up by her gynecologist and treated using a topical corticoid for chronic eczema albeit with no improvement. She was referred to this department where a diagnosis of Paget's disease of the breast associated with a ductal carcinoma in situ was made. Paget's disease is uncommon prior to the fourth decade of life and the great majority of cases are associated with breast carcinomas. Differential diagnosis must be made between this condition and nipple eczema. As shown in the present case report, late diagnosis results in poor prognosis and higher morbidity since mutilating procedures then become necessary.