Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas.

Invasion of surrounding stroma is an early event in breast cancer metastatic progression, and involves loss of cell polarity, loss of myoepithelial layer, epithelial-mesenchymal transition (EMT) and remodeling of the extracellular matrix (ECM). Integrins are transmembrane receptors responsible for cell-ECM binding, which triggers signals that regulate many aspects of cell behavior and fate. Changes in the expression, localization and pairing of integrins contribute for abnormal responses found in transformed epithelia. We analyzed 345 human breast cancer samples in tissue microarrays (TMA) from cases diagnosed with invasive breast carcinoma to assess the expression and localization pattern of integrin αV and correlation with clinical parameters. Patients with lower levels of integrin αV staining showed reduced cancer specific survival. A subset of cases presented a peripheral staining of integrin αV surrounding tumor cell clusters, possibly matching the remaining myoepithelial layer. Indeed, the majority of ductal carcinoma in situ (DCIS) components found in the TMA presented integrin αV at their periphery, whereas this pattern was mostly lost in invasive components, even in the same sample. The lack of peripheral integrin αV correlated with decreased cancer specific survival. In addition, we observed that the presence of integrin αV in the stroma was an indicative of poor survival and metastatic disease. Consistently, by interrogating publicly available datasets we found that, although patients with higher mRNA levels of integrin αV had increased risk of developing metastasis, high co-expression of integrin αV and a myoepithelial cell marker (MYH11) mRNA levels correlated with better clinical outcomes. Finally, a 3D cell culture model of non-malignant and malignant cells reproduced the integrin αV pattern seen in patient samples. Taken together, our data indicate that both the expression levels of integrin αV and its tissue localization in primary tumors have prognostic value, and thus, could be used to help predict patients at higher risk of developing metastasis.

Benefits of a standardized protocol for axillary management after neoadjuvant chemotherapy in a single center

Introduction: The axillary lymph node status is one of the most important prognostic factors in breast cancer. For locally advanced tumors, neoadjuvant chemotherapy favors higher rates of breast lumpectomy and downstaging tumor burden of axilla. The aim of this study was to evaluate the use of a standardized image-guided protocol after neoadjuvant chemotherapy to enable sentinel node dissection in patients with axillary downstaging, avoiding axillary dissection. Methods: Retrospective cohort study of data collected from medical records of patients who underwent neoadjuvant chemotherapy in a single center, from January 2014 to December 2018. The protocol comprises the placement of a metal clip in positive axillary lymph node, in patients with up to two clinically abnormal lymph nodes presented on imaging. After neoadjuvant chemotherapy, and once a radiologic complete response was achieved, sentinel node dissection was performed using blue dye and radiotracer. Axillary dissection were avoided in patients whose clipped sentinel node were negative for metastasis and in patients with three identified and negative sentinel node dissection. Results: A total of 471 patients were analyzed for this study: 303 before and 165 after the implementation of the protocol; 3 cases were excluded. The rate of sentinel node dissection in clinical nodes positive patients was statistically higher in this group when compared to patients treated before the protocol implementation (22.8% vs. 40.8%; p=0.001). Patients with triple negative and HER2-positive tumors underwent sentinel node dissection more frequently when compared to luminal tumors (p=0.03). After multivariate analysis, the variables that were associated with a greater chance of performing sentinel node dissection were clinical staging, type of surgery performed and implementation of the axillary assessment protocol. Conclusions: The results showed that the use of an easily and accessible image-guided protocol can improve sentinel node dissection in selected patients, even if the lymph node was positive previously to neoadjuvant treatment.

Genetic Landscape of Male Breast Cancer.

Male breast cancer (MBC) is now considered molecularly different from female breast cancer (FBC). Evidence from studies indicates that common genetic and epigenetic features of FBC are not shared with those diagnosed in men. Genetic predisposition is likely to play a significant role in the tumorigenesis of this rare disease. Inherited germline variants in BRCA1 and BRCA2 account for around 2% and 10% of MBC cases, respectively, and the lifetime risk of breast cancer for men harboring BRCA1 and BRCA2 mutations is 1.2% and 6.8%. As for FBC, pathogenic mutations in other breast cancer genes have also been recently associated with an increased risk of MBC, such as PALB2 and CHEK2 mutations. However, while multigene germline panels have been extensively performed for BC female patients, the rarity of MBC has resulted in limited data to allow the understanding of the magnitude of risk and the contribution of recently identified moderate penetrance genes of FBC for MBC predisposition. This review gathers available data about the germline genetic landscape of men affected by breast cancer, estimated risk associated with these genetic variants, and current guidelines for clinical management.

Pleomorphic adenoma of the breast

Pleomorphic adenoma (PA) is a common tumor of the salivary gland, but rarely occurs in the breast. PA of the breast is a benign tumor that usually presents as a periareolar nodule. Core-needle biopsies may yield misdiagnosis with complex fibroadenoma, phyllodes tumor and metaplastic breast cancer due to the mixture of stromal and epithelial elements. We present a case of PA of the breast suspected after core-needle biopsy, but confirmed after surgical excision. The importance to make a correct diagnosis consists in avoid extensive unnecessary surgery, such as mastectomy, since PA can be treated with local surgical resection.

Deep Learning Predicts Underlying Features on Pathology Images with Therapeutic Relevance for Breast and Gastric Cancer.

DNA repair deficiency (DRD) is an important driver of carcinogenesis and an efficient target for anti-tumor therapies to improve patient survival. Thus, detection of DRD in tumors is paramount. Currently, determination of DRD in tumors is dependent on wet-lab assays. Here we describe an efficient machine learning algorithm which can predict DRD from histopathological images. The utility of this algorithm is demonstrated with data obtained from 1445 cancer patients. Our method performs rather well when trained on breast cancer specimens with homologous recombination deficiency (HRD), AUC (area under curve) = 0.80. Results for an independent breast cancer cohort achieved an AUC = 0.70. The utility of our method was further shown by considering the detection of mismatch repair deficiency (MMRD) in gastric cancer, yielding an AUC = 0.81. Our results demonstrate the capacity of our learning-base system as a low-cost tool for DRD detection.

High CD90 (THY-1) expression positively correlates with cell transformation and worse prognosis in basal-like breast cancer tumors.

Breast cancer is the most prevalent cancer among women, with the basal-like triple negative (TNBC) being the most agressive one, displaying the poorest prognosis within the ductal carcinoma subtype. Due to the lack of adequate molecular targets, the diagnosis and treatment of patients with the TNBC phenotype has been a great challenge. In a previous work, we identified CD90/Thy-1 as being highly expressed in the aggressive high malignancy grade Hs578T basal-like breast tumor cell line, pointing to this molecule as a promising breast tumor marker, which should be further investigated. Here, CD90 expression was analyzed in human breast cancer samples and its functional role was investigated to better assess the oncogenic nature of CD90 in mammary cells. Quantification of CD90 expression in human breast cancer samples, by tissue microarray, showed that high CD90 positivity correlates with metastasis and poor patient survival in the basal-like subtype. The functional genetic approach, by overexpression in the CD90 cDNA in a basal-like normal mammary cell line (MCF10A) and knockdown in a highly malignant cell line (Hs578T), allowed us to demonstrate that CD90 is involved with several cellular processes that lead to malignant transformation, such as: morphological change, increased cell proliferation, invasiveness, metastasis and activation of the EGFR pathway. Therefore, our results reveal that CD90 is involved with malignant transformation in breast cancer cell lines and is correlated with metastasis and poor patient survival in the basal-like subtype, being considered as a promising new breast cancer target.

Can diffusion-weighted imaging add information in the evaluation of breast lesions considered suspicious on magnetic resonance imaging?

OBJECTIVE: To assess the role of diffusion-weighted imaging (DWI) in the evaluation of breast lesions classified as suspicious on magnetic resonance imaging (MRI), correlating the findings with the results of the histological analysis. MATERIALS AND METHODS: This was a retrospective, descriptive study based on a review of the medical records of 215 patients who were submitted to MRI with DWI before undergoing biopsy at a cancer center. Apparent diffusion coefficient (ADC) values were calculated for each lesion, and the result of the histological analysis was considered the gold standard. RESULTS: The mean age was 49 years. We identified 252 lesions, 161 (63.9%) of which were found to be malignant in the histological analysis. The mean ADC value was higher for the benign lesions than for the malignant lesions (1.50 × 10-3 mm2/s vs. 0.97 × 10-3 mm2/s), the difference being statistically significant (p < 0.001). The ADC cut-off point with the greatest sensitivity and specificity on the receiver operating characteristic curve was 1.03 × 10-3 mm2/s. When the DWI and conventional MRI findings were combined, the accuracy reached 95.9%, with a sensitivity of 95.7% and a specificity of 96.4%. CONCLUSION: The use of DWI could facilitate the characterization of breast lesions, especially those classified as BI-RADS 4, increasing the specificity and diagnostic accuracy of MRI.

OBJETIVO: Avaliar o papel da sequência em difusão na avaliação de lesões mamárias suspeitas na ressonância magnética (RM), correlacionando seus achados com os resultados histológicos. MATERIAIS E MÉTODOS: Foi realizado estudo retrospectivo, descritivo, baseado na análise de prontuários médicos de 215 pacientes que realizaram RM com sequência em difusão e que foram submetidas a biópsia em um centro de referência oncológico. Foi calculado o valor do coeficiente de difusão aparente (ADC ­ apparent diffusion coefficient) para cada lesão e o resultado histológico foi considerado como padrão ouro. RESULTADOS: A idade média das pacientes foi 49 anos. Foram identificadas 252 lesões, e destas, 161 (63,9%) eram lesões malignas na avaliação histológica. A média obtida do valor do ADC nas lesões benignas (1,50 × 10­3 mm2/s) foi superior à média das lesões malignas (0,97 × 10­3 mm2/s), com significância estatística (p < 0,001). O ponto de corte com maior sensibilidade e especificidade pela curva receiver operating characteristic foi 1,03 × 10­3 mm2/s. Com a combinação da difusão com os achados da RM, a acurácia chegou a 95,9%, com sensibilidade de 95,7% e especificidade de 96,4%. CONCLUSÃO: O uso da sequência em difusão pode auxiliar na caracterização das lesões mamárias, principalmente daquelas classificadas como BI-RADS 4, aumentando a especificidade e a acurácia diagnóstica da RM.

Can diffusion-weighted imaging add information in the evaluation of breast lesions considered suspicious on magnetic resonance imaging? / A difusão pode acrescentar informações na avaliação de lesões mamárias suspeitas na ressonância magnética?

Abstract Objective: To assess the role of diffusion-weighted imaging (DWI) in the evaluation of breast lesions classified as suspicious on magnetic resonance imaging (MRI), correlating the findings with the results of the histological analysis. Materials and Methods: This was a retrospective, descriptive study based on a review of the medical records of 215 patients who were submitted to MRI with DWI before undergoing biopsy at a cancer center. Apparent diffusion coefficient (ADC) values were calculated for each lesion, and the result of the histological analysis was considered the gold standard. Results: The mean age was 49 years. We identified 252 lesions, 161 (63.9%) of which were found to be malignant in the histological analysis. The mean ADC value was higher for the benign lesions than for the malignant lesions (1.50 × 10-3 mm2/s vs. 0.97 × 10−3 mm2/s), the difference being statistically significant (p < 0.001). The ADC cut-off point with the greatest sensitivity and specificity on the receiver operating characteristic curve was 1.03 × 10−3 mm2/s. When the DWI and conventional MRI findings were combined, the accuracy reached 95.9%, with a sensitivity of 95.7% and a specificity of 96.4%. Conclusion: The use of DWI could facilitate the characterization of breast lesions, especially those classified as BI-RADS 4, increasing the specificity and diagnostic accuracy of MRI.

Resumo Objetivo: Avaliar o papel da sequência em difusão na avaliação de lesões mamárias suspeitas na ressonância magnética (RM), correlacionando seus achados com os resultados histológicos. Materiais e Métodos: Foi realizado estudo retrospectivo, descritivo, baseado na análise de prontuários médicos de 215 pacientes que realizaram RM com sequência em difusão e que foram submetidas a biópsia em um centro de referência oncológico. Foi calculado o valor do coeficiente de difusão aparente (ADC - apparent diffusion coefficient) para cada lesão e o resultado histológico foi considerado como padrão ouro. Resultados: A idade média das pacientes foi 49 anos. Foram identificadas 252 lesões, e destas, 161 (63,9%) eram lesões malignas na avaliação histológica. A média obtida do valor do ADC nas lesões benignas (1,50 × 10-3 mm2/s) foi superior à média das lesões malignas (0,97 × 10-3 mm2/s), com significância estatística (p < 0,001). O ponto de corte com maior sensibilidade e especificidade pela curva receiver operating characteristic foi 1,03 × 10-3 mm2/s. Com a combinação da difusão com os achados da RM, a acurácia chegou a 95,9%, com sensibilidade de 95,7% e especificidade de 96,4%. Conclusão: O uso da sequência em difusão pode auxiliar na caracterização das lesões mamárias, principalmente daquelas classificadas como BI-RADS 4, aumentando a especificidade e a acurácia diagnóstica da RM.

Lobular Carcinoma in Situ with Atypical Mass Presentation: a Case Report.

Lobular carcinoma in situ (LCIS) is associated with an increased risk of breast cancer and accounts for 1 to 2% of all breast cancers. LCIS diagnosis currently remains one of the major identifiable risk factors for subsequent breast cancer development. Imaging methods are becoming increasingly sensitive, and the consequent detection of small lesions and subtle abnormalities increases the chance of detection of in situ and invasive carcinomas, leading to a reduction in mortality. This report describes a case of a palpable complaint with abnormal imaging findings, including a solid LCIS mass.

Lobular Carcinoma in Situ with Atypical Mass Presentation: a Case Report / Carcinoma lobular in situ com apresentação nodular atípica: relato de caso

Lobular carcinoma in situ (LCIS) is associated with an increased risk of breast cancer and accounts for 1 to 2% of all breast cancers. LCIS diagnosis currently remains one of the major identifiable risk factors for subsequent breast cancer development. Imaging methods are becoming increasingly sensitive, and the consequent detection of small lesions and subtle abnormalities increases the chance of detection of in situ and invasive carcinomas, leading to a reduction in mortality. This report describes a case of a palpable complaint with abnormal imaging findings, including a solid LCIS mass.

O Carcinoma Lobular in situ (CLIS) está associado a um aumento do risco de câncer de mama e representa 1-2% de todas as neoplasias mama. Atualmente, o diagnóstico de CLIS continua a ser um dos maiores fatores de risco identificáveis para o posterior desenvolvimento de câncer de mama. Os métodos de imagem estão cada vez mais sensíveis, fazendo com que a detecção de pequenas lesões e anormalidade sutis aumentemo risco de detecções de carcinomas in situ e invasivos, levando a diminuição da mortalidade. Neste relato será descrito um caso de queixa clínica palpável com alteração de achados de imagem como massa sólida de CLIS.

The breast cancer immunophenotype of TP53-p.R337H carriers is different from that observed among other pathogenic TP53 mutation carriers.

Germline TP53 mutations are associated with Li-Fraumeni syndrome, an autosomal dominant disorder characterized by a predisposition to multiple early-onset cancers including breast cancer (BC), the most prevalent tumor among women. The majority of germline TP53 mutations are clustered within the DNA-binding domain of the gene, disrupting the structure and function of the protein. A specific germline mutation in the tetramerization domain of p53, p.R337H, was reported at a high frequency in Southern and Southeastern Brazil. This mutation appears to result in a more subtle defect in the protein, which becomes functionally deficient only under particular conditions. Recent studies show that the BC phenotype in TP53 mutation carriers is often HER2 positive (63-83%). Considering that the immunophenotype of BC among p.R337H carriers has not been reported, we reviewed immunohistochemistry data of 66 p.R337H carriers in comparison with 12 patients with other non-functional TP53 germline mutation. Although 75% of carriers of these mutations showed significant HER2 overexpression (3+), corroborating previous studies, only 22.7% of p.R337H patients had BC overexpressing HER2. These results reinforce the notion that different germline mutations in TP53 may predispose to BC via different mechanisms.

Correlation between PET/CT results and histological and immunohistochemical findings in breast carcinomas / Correlação entre resultado do PET/CT e achados histológicos e imuno-histoquímicos em carcinomas mamários

Objective To correlate the results of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) performed with a specific protocol for assessment of breasts with histological/immunohistochemical findings in breast carcinoma patients. Materials and Methods Cross-sectional study with prospective data collection, where patients with biopsy-confirmed breast carcinomas were studied. The patients underwent PET/CT examination in prone position, with a specific protocol for assessment of breasts. PET/CT findings were compared with histological and immunohistochemical data. Results The authors identified 59 malignant breast lesions in 50 patients. The maximum diameter of the lesions ranged from 6 to 80 mm (mean: 32.2 mm). Invasive ductal carcinoma was the most common histological type (n = 47; 79.7%). At PET/CT, 53 (89.8%) of the lesions demonstrated anomalous concentrations of 18F-FDG, with maximum SUV ranging from 0.8 to 23.1 (mean: 5.5). A statistically significant association was observed between higher values of maximum SUV and histological type, histological grade, molecular subtype, tumor diameter, mitotic index and Ki-67 expression. Conclusion PET/CT performed with specific protocol for assessment of breasts has demonstrated good sensitivity and was associated with relevant histological/immunohistochemical factors related to aggressiveness and prognosis of breast carcinomas. .

Objetivo Correlacionar o resultado da tomografia por emissão de pósitrons/tomografia computadorizada (PET/CT) com 18F-flúor-2-deoxi-D-glicose (18F-FDG) realizado com protocolo específico para avaliação das mamas com achados histológicos/imuno-histoquímicos em pacientes com carcinomas mamários. Materiais e Métodos Estudo transversal, com coleta prospectiva dos dados, em que foram estudadas pacientes com carcinomas mamários confirmados por biópsia. As pacientes incluídas foram submetidas a exame de PET/CT realizado em decúbito ventral, com protocolo específico para avaliação das mamas. Os achados do PET/CT foram comparados aos dados histológicos e imuno-histoquímicos. Resultados Foram identificadas 59 lesões mamárias malignas nas 50 pacientes incluídas no estudo. O diâmetro máximo das lesões variou de 6 a 80 mm (média : 32,2 mm). O tipo histológico mais comum foi o carcinoma ductal invasivo (n = 47; 79,7%). No PET/CT, 53 (89,8%) destas lesões apresentaram concentração anômala de 18F-FDG, com SUV máximo variando de 0,8 a 23,1 (média: 5,5). Houve associação estatisticamente significante entre maiores valores de SUV máximo e tipo histológico, grau histológico, subtipo molecular, diâmetro do tumor, índice mitótico e expressão de Ki-67. Conclusão O PET/CT realizado com protocolo específico para avaliação das mamas demonstrou boa sensibilidade e apresentou associação com importantes fatores histológicos/imuno-histoquímicos relacionados à agressividade e prognóstico dos carcinomas mamários. .

NF-κB and COX-2 expression in nonmalignant endometrial lesions and cancer.

OBJECTIVES: To examine the immunohistochemical expression of cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) in benign endometrial polyps (EPs), endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and endometrioid endometrial cancer (EC). METHODS: The immunohistochemical expression of COX-2 and NF-κB was performed using an Aperio Scanscope XT automated system in 218 patients with endometrioid EC and 107 patients with nonmalignant endometrial lesions: 53 with benign EPs, 37 with EH, and 17 with EIN. RESULTS: COX-2 and NF-κB p50 expression were significantly lower in EC compared with nonmalignant lesions. We observed significant decreased NF-κB p65 expression in EC vs EPs (P < .001) and EH (P = .014) as well as in EIN vs. EPs (P = .01). For patients with EC, COX-2 correlated positively with NF-κB p65 and NF-κB p50 (P < .001). Grade 3 tumors had a higher mean expression of NF-κB p65 (P = .03). NF-κB p50, NF-κB p65, and COX-2 expression had no impact on survival. CONCLUSIONS: We conclude that COX-2 and NF-κB expression are lower in EC compared with nonmalignant endometrial lesions. COX-2 and NF-κB expression have no prognostic value in EC.

Correlation between PET/CT results and histological and immunohistochemical findings in breast carcinomas.

OBJECTIVE: To correlate the results of (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) performed with a specific protocol for assessment of breasts with histological/immunohistochemical findings in breast carcinoma patients. MATERIALS AND METHODS: Cross-sectional study with prospective data collection, where patients with biopsy-confirmed breast carcinomas were studied. The patients underwent PET/CT examination in prone position, with a specific protocol for assessment of breasts. PET/CT findings were compared with histological and immunohistochemical data. RESULTS: The authors identified 59 malignant breast lesions in 50 patients. The maximum diameter of the lesions ranged from 6 to 80 mm (mean: 32.2 mm). Invasive ductal carcinoma was the most common histological type (n = 47; 79.7%). At PET/CT, 53 (89.8%) of the lesions demonstrated anomalous concentrations of (18)F-FDG, with maximum SUV ranging from 0.8 to 23.1 (mean: 5.5). A statistically significant association was observed between higher values of maximum SUV and histological type, histological grade, molecular subtype, tumor diameter, mitotic index and Ki-67 expression. CONCLUSION: PET/CT performed with specific protocol for assessment of breasts has demonstrated good sensitivity and was associated with relevant histological/immunohistochemical factors related to aggressiveness and prognosis of breast carcinomas.

OBJETIVO: Correlacionar o resultado da tomografia por emissão de pósitrons/tomografia computadorizada (PET/CT) com 18F-flúor-2-deoxi-D-glicose (18F-FDG) realizado com protocolo específico para avaliação das mamas com achados histológicos/imuno-histoquímicos em pacientes com carcinomas mamários. MATERIAIS E MÉTODOS: Estudo transversal, com coleta prospectiva dos dados, em que foram estudadas pacientes com carcinomas mamários confirmados por biópsia. As pacientes incluídas foram submetidas a exame de PET/CT realizado em decúbito ventral, com protocolo específico para avaliação das mamas. Os achados do PET/CT foram comparados aos dados histológicos e imuno-histoquímicos. RESULTADOS: Foram identificadas 59 lesões mamárias malignas nas 50 pacientes incluídas no estudo. O diâmetro máximo das lesões variou de 6 a 80 mm (média : 32,2 mm). O tipo histológico mais comum foi o carcinoma ductal invasivo (n = 47; 79,7%). No PET/CT, 53 (89,8%) destas lesões apresentaram concentração anômala de 18F-FDG, com SUV máximo variando de 0,8 a 23,1 (média: 5,5). Houve associação estatisticamente significante entre maiores valores de SUV máximo e tipo histológico, grau histológico, subtipo molecular, diâmetro do tumor, índice mitótico e expressão de Ki-67. CONCLUSÃO: O PET/CT realizado com protocolo específico para avaliação das mamas demonstrou boa sensibilidade e apresentou associação com importantes fatores histológicos/imuno-histoquímicos relacionados à agressividade e prognóstico dos carcinomas mamários.

Identificação e validação de marcadores moleculares das vias de sinalização WNT, PI3K e processo EMT para risco de progressão de carcinoma ductal in situ de mama / Identification and validation of molecular markers of WNT and PI3K signaling pathway and EMT process for the risk of progression of ductal carcinoma in situ of the breast

O carcinoma ductal da mama é o tipo histológico mais freqüente, sendo que o in situ (CDIS) representa uma neoplasia com incidência crescente, devido aos métodos de detecção precoce de lesões mamárias não palpáveis. Essa neoplasia da mama inclui um grupo heterogêneo de tumores pré-invasivos, com potencial maligno distinto, que podem progredir rapidamente para a forma invasiva, ou não apresentarem evolução, após um longo período da doença. Um estudo prévio (CASTRO et al. 2008) aplicou o conceito de divergência molecular em grupos de lesões que mimetizam a progressão do câncer de mama [epitélio normal (EN), carcinoma ductal in situ (CDIS) puro, componente in situ de lesão que coexiste com invasão (CDIS-CDI) e do carcinoma ductal invasivo (CDI)], utilizando as metodologias de microdissecção a laser e cDNA microarray. O padrão de expressão gênica do grupo de células epiteliais tumorais do componente in situ do CDIS-CDI é semelhante ao grupo de células tumorais do CDI e diferente do grupo de células CDIS puro, cujos aspectos morfológicos são semelhantes ao componente in situ do CDIS-CDI. Isso sugeriu que as modificações moleculares das células do componente in situ do CDIS-CDI, já estejam presentes antes da manifestação morfológica de invasão e que os genes diferentemente expressos entre os dois grupos de células de lesões pré-invasivas, sejam potenciais preditores de risco de progressão do CDIS puro. Assim, nós avaliamos 28 genes das vias de sinalização WNT, PI3K e processo EMT, previamente selecionados do estudo anterior (CASTRO et al. 2008) através de RT-PCR quantitativo (RT-qPCR), em células tumorais capturadas de amostras congeladas do CDIS puro e do componente in situ do CDIS-CDI. Esse trabalho confirmou a diferença de expressão em células epiteliais entre os dois grupos de lesões pré-invasivas, em 14 (70%) de 20 genes avaliados, que apresentaram dados confiáveis nos ensaios de TLDA, sendo que 13 genes apresentaram maior expressão em CDIS...

Among breast tumors, ductal breast carcinoma is the most common histologic type. Ductal carcinoma in situ (DCIS) has increasing incidence, mainly due to early detection methods of non-palpable breast lesions. DCIS includes a heterogeneous group of pre-invasive tumors, with distinct malignant potential, which can either rapidly progress to the invasive form, or show no progression after a long period of surveillance. In a previous study from the group (CASTRO et al. 2008) based on the expression pattern of epithelial cells, using laser capture microdissection and cDNA microarray, the concept of molecular divergence was applied to groups of breast lesions which mimic the progression of breast cancer [cells from normal epithelium, cells from pure ductal carcinoma in situ (DCIS), cells from in situ component that coexists with invasive lesion (DCIS-IDC) and cells from invasive ductal carcinoma (IDC)]. The gene expression pattern of the cells from the in situ component of DCIS-IDC is more similar to the group of IDC tumor cells other than to the group of pure DCIS of cells, which presents higher similarity in terms of morphological features to the in situ component of DCIS-IDC. This suggests that the molecular changes of the cells from the in situ component of DCIS-IDC are already present before morphological manifestations of invasion and that the genes differentially expressed between the two groups of cells of pre-invasive lesions, are potential predictors of risk of progression of pure DCIS. Thus, we evaluated 28 previously selected genes of WNT signaling pathway, PI3K and EMT process (CASTRO et al. 2008) by quantitative RT-PCR (RT-qPCR) in tumor cells captured from in situ lesions of pure DCIS and DCIS-IDC from frozen samples. This work confirmed the difference in expression of epithelial cells between the two groups of preinvasive lesions, in 14 (70%) of the 20 genes evaluated, by reliable TLDA assays. Most genes (13 genes) showed higher expression in pure...

Avaliação de resposta patológica em câncer de mama após quimioterapia neoadjuvante: padronização de protocolo adaptado / Assessment of pathological response in breast cancer after neoadjuvant chemotherapy: standardization of adapted protocol

O conceito de resposta patológica completa (pCR) é controverso. Estudos prévios utilizaram diferentes métodos de avaliação da pCR, porém não há um consenso universal sobre o melhor protocolo para o estudo das peças cirúrgicas de pacientes portadoras de carcinoma mamário submetidas ao tratamento quimioterápico neoadjuvante. Symmans et al. desenvolveram um sistema de classificação de carga residual de câncer (RCB) de mama após quimioterapia neoadjuvante, analisando a dimensão do leito tumoral primário, a porcentagem de células neoplásicas viáveis residuais no leito tumoral e o comprometimento linfonodal. Apresentamos uma proposta de avaliação da resposta patológica nos tumores de mama após quimioterapia neoadjuvante, por meio de um protocolo adaptado à nossa rotina de exame anatomopatológico de peças cirúrgicas, com base no estudo de Symmans et al.

The concept of pathologic complete response (pCR) is controversial. Previous studies used different methods of pCR assessment, but there is no universal consensus about the best protocol for the study of surgical specimens from patients with breast carcinoma undergoing neoadjuvant chemotherapy. Symmans et al. developed a classification system of residual cancer burden (RCB) after neoadjuvant chemotherapy for breast cancer analyzing the extent of primary tumor bed, the percentage of residual viable tumor cells in the tumor bed and lymph node involvement. We present a proposal for the evaluation of pathological response in breast tumors after neoadjuvant chemotherapy. Based on Symmans et al. study, it consists in a protocol adapted to our routine pathological examination of surgical specimens.

Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast.

Alterations in the gene expression profile in epithelial cells during breast ductal carcinoma (DC) progression have been shown to occur mainly between pure ductal carcinoma in situ (DCIS) to the in situ component of a lesion with coexisting invasive ductal carcinoma (DCIS-IDC) implying that the molecular program for invasion is already established in the preinvasive lesion. For assessing early molecular alterations in epithelial cells that trigger tumorigenesis and testing them as prognostic markers for breast ductal carcinoma progression, we analyzed, by reverse transcription-quantitative polymerase chain reaction, eight genes previously identified as differentially expressed between epithelial tumor cells populations captured from preinvasive lesions with distinct malignant potential, pure DCIS and the in situ component of DCIS-IDC. ANAPC13 and CLTCL1 down-regulation revealed to be early events of DC progression that anticipated the invasiveness manifestation. Further down-regulation of ANAPC13 also occurred after invasion appearance and the presence of the protein in invasive tumor samples was associated with higher rates of overall and disease-free survival in breast cancer patients. Furthermore, tumors with low levels of ANAPC13 displayed increased copy number alterations, with significant gains at 1q (1q23.1-1q32.1), 8q, and 17q (17q24.2), regions that display common imbalances in breast tumors, suggesting that down-regulation of ANAPC13 contributes to genomic instability in this disease.

Comparação de três modelos matemáticos para predição de metástases em linfonodos não sentinela em pacientes com câncer de mama e linfonodo sentinela positivo / Comparison of three mathematical models for prediction of non-sentinel lymph node metastasis in patients with breast cancer and positive sentinel lymph node

Objetivo: foi comparar um "Nomograma Brasileiro" desenvolvido para este estudo com o "Nomograma do Memorial Sloan Kettering Câncer Center" e o Stanford Online Calculator na predição de metástases em linfonodos não sentinela em um mesmo grupo populacional de pacientes brasileiras com câncer de mama e linfonodo sentinela positivo. Métodos: foram incluídas 261 pacientes com resultado positivo na biópsia do linfonodo sentinela e submetidas ao esvaziamento axilar em dois centros brasileiros de tratamento de câncer de mama, das quais 92 (35%) apresentaram metástases em linfonodos não sentinela. O "Nomograma Brasileiro", e o "Nomograma do Memorial Sloan Kettering Câncer Center" e o Stanford Online Calculator foram aplicados para calcular a probabilidade de metástases em linfonodos não sentinela. A acurácia de cada modelo foi calculada pela área sob a curva ROC (AUC). Resultados: o "Nomograma Brasileiro", e o "Nomograma do Memorial Sloan Kettering Câncer Center" e o Stanford Online Calculator apresentaram valores da AUC de 0,694 (IC95%0,629-0,760; p<0,0001), 0,626 (IC95% 0,555-0,697; p<0,001) e 0,619 (IC95% 0,548 -689;p=0,002), respectivamente. Conclusões: os três modelos apresentaram uma discriminação razoável na predição de metástases em linfonodos não sentinela em pacientes com câncer de mama. O "Nomograma Brasileiro apresentou a melhor acurácia entre os modelos testados, mas precisa ser validado em populações de pacientes diferentes daquelas utilizadas em sua construção.

Embryonal rhabdomyosarcoma of the uterine cervix in a 47-year-old woman.

Embryonal rhabdomyosarcoma (RMS) of the female genital tract usually occurs in the vagina during childhood. The uterine cervix as a primary site is rare, but is more frequent until the second decade of life. It usually has a good prognosis and the treatment is based on multidrug chemotherapy, radiotherapy and surgery. RMS accounts for <5% of all adult soft tissue sarcomas. Previous reports that included all primary sites showed a poorer five-year disease specific survival for adults with RMS when compared to the pediatric population. This difference has been attributed to a higher proportion of adverse prognostic clinical and pathological factors, and to inadequate treatment given to adults with RMS. A total of 115 patients with cervical embryonal RMS have previously been described; however, only 10 cases were reported in women older than 40 years. We present a 47-year-old woman treated with radical hysterectomy followed by adjuvant chemotherapy and review the current literature.