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Peritoneal washing cytology (CY) in patients with pancreatic cancer is mainly used for staging; however, it may also be used to evaluate the intraperitoneal status to predict a more accurate prognosis. Here, we investigated the potential of deep learning of CY specimen images for predicting the 1-year prognosis of pancreatic cancer in CY-positive patients. CY specimens from 88 patients with prognostic information were retrospectively analyzed. CY specimens scanned by the whole slide imaging device were segmented and subjected to deep learning with a Vision Transformer (ViT) and a Convolutional Neural Network (CNN). The results indicated that ViT and CNN predicted the 1-year prognosis from scanned images with accuracies of 0.8056 and 0.8009 in the area under the curve of the receiver operating characteristic curves, respectively. Patients predicted to survive 1 year or more by ViT showed significantly longer survivals by Kaplan-Meier analyses. The cell nuclei found to have a negative prognostic impact by ViT appeared to be neutrophils. Our results indicate that AI-mediated analysis of CY specimens can successfully predict the 1-year prognosis of patients with pancreatic cancer positive for CY. Intraperitoneal neutrophils may be a novel prognostic marker and therapeutic target for CY-positive patients with pancreatic cancer.
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Aprendizado Profundo , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/diagnóstico , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Redes Neurais de Computação , Curva ROC , Citodiagnóstico/métodos , Estimativa de Kaplan-Meier , Adulto , Lavagem Peritoneal , Idoso de 80 Anos ou mais , Neutrófilos/patologia , CitologiaRESUMO
Patients with Crohn's disease are at higher risk of opportunistic infection, especially if treated with immunosuppressive therapy. Cytomegalovirus has been reported to cause ulcerated lesions mainly in the lower gastrointestinal tract of inflammatory bowel disease patients. We herein report a rare case of Crohn's disease complicated with cytomegalovirus esophagitis, which was difficult to distinguish from exacerbation of Crohn's disease. Diagnostic values of clinical course, blood tests, endoscopic and histological examinations are limited but the present case was therapeutically diagnosed by antiviral therapy in combination with histological evidence of cytomegalovirus.
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Doença de Crohn , Infecções por Citomegalovirus , Esofagite , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/complicações , Esofagite/virologia , Esofagite/diagnóstico , Esofagite/tratamento farmacológico , Diagnóstico Diferencial , Antivirais/uso terapêutico , Masculino , Feminino , Adulto , Progressão da DoençaRESUMO
INTRODUCTION: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. METHODS: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis. RESULTS: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. CONCLUSION: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.
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Neoplasias da Mama , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Feminino , Biópsia por Agulha Fina/métodos , Biópsia Líquida , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Citodiagnóstico/métodos , Tumor Filoide/patologia , Tumor Filoide/genética , Tumor Filoide/diagnóstico , Fibroadenoma/patologia , Fibroadenoma/genética , Fibroadenoma/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/diagnóstico , Pessoa de Meia-Idade , CitologiaRESUMO
BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC. METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy. RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis. CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Lobular/patologia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Carcinoma Ductal de Mama/patologia , Resultado do Tratamento , Microambiente TumoralRESUMO
We previously reported on two women with breast lesions in whom radiological examination could not exclude malignancy. In both cases, mastectomy was performed, and histological analyses revealed papillary lesions lined by fibrovascular stroma and nuclear inverse polarity. Hematoxylin-eosin, p63, and calponin staining indicated an absence of myoepithelial cells. However, it was concluded that the lesions had been non-malignant. These women have now been under long-term surveillance (74 months for one case and 62 months for the other) and have had no disease recurrence. Mucin (MUC)1, MUC2, MUC4, MUC5AC, MUC5B, and MUC6 immunostaining has also been performed in these women to investigate further whether their tumors were malignant or benign. In both cases, the tumors were only positive for MUC1 in apical luminal apical cells, as in normal breast tissue. MUC5B immunostaining, even when weak, can detect early breast cancer but was completely negative in our two cases. Therefore, both tumors were considered benign. Our findings in these cases suggest that nuclear inverse polarity papillary lesions lacking myoepithelial cells are benign. This knowledge should decrease the number of unnecessary operations performed for this tumor and their negative impact on patients' quality of life.
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Neoplasias da Mama , Mucinas , Humanos , Feminino , Neoplasias da Mama/patologia , Qualidade de Vida , Mastectomia , Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia , Mucina-1RESUMO
Consultation by subspecialty experts is the most common mode of rendering diagnosis in challenging cases in pathological practice. Our study aimed to highlight the diagnostic benefits of whole-slide image (WSI)-based remote consultation. We obtained diagnostically challenging cases from two institutions from the years 2010 and 2013, with histological diagnoses that contained keywords "probable," "suggestive," "suspicious," "inconclusive," and "uncertain." A total of 270 cases were selected for remote consultation using WSIs scanned at 40 × . The consultation process consisted of three rounds: the first and second rounds each with 12 subspecialty experts and the third round with six multi-expertise senior pathologists. The first consultation yielded 44% concordance, and a change in diagnosis occurred in 56% of cases. The most frequent change was from inconclusive to definite diagnosis (30%), followed by minor discordance (14%), and major discordance (12%). Out of the 70 cases which reached the second round, 31 cases showed discrepancy between the two consultants. For these 31 cases, a consensus diagnosis was provided by six multi-expertise senior pathologists. Combining all WSI-based consultation rounds, the original inconclusive diagnosis was changed in 140 (52%) out of 266 cases. Among these cases, 80 cases (30%) upgraded the inconclusive diagnosis to a definite diagnosis, and 60 cases (22%) changed the diagnosis with major or minor discordance, accounting for 28 cases (10%) and 32 cases (12%), respectively. We observed significant improvement in the pathological diagnosis of difficult cases by remote consultation using WSIs, which can further assist in patient healthcare. A post-study survey highlighted various benefits of WSI-based consults.
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Patologia Cirúrgica , Consulta Remota , Telepatologia , Humanos , Microscopia/métodos , Patologia Cirúrgica/métodos , Consulta Remota/métodos , Telepatologia/métodosRESUMO
Preoperative diagnosis with multimodal approaches might lead to overtreatment. Cautious understanding of cytology and dynamic contrast-enhanced magnetic resonance imaging is required when a Kuttner tumor is cited as differential diagnosis.
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Chemotherapy for multiple primary malignancies is challenging. We herein report a case of synchronous primary lung adenocarcinoma and hepatocellular carcinoma (HCC). A 72-year-old man was admitted for the evaluation of an abnormal shadow on his lung. Computed tomography revealed a lung nodule in the right upper lobe and multiple liver masses. He was diagnosed with synchronous primary lung adenocarcinoma and HCC. Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) chemotherapy was efficacious for both tumors. ABCP chemotherapy may be a potential treatment option for synchronous primary lung adenocarcinoma and HCC.
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Adenocarcinoma de Pulmão , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/tratamento farmacológico , Paclitaxel/uso terapêuticoRESUMO
In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.
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Neoplasias da Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Amplificação de Genes , Mutação , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Adulto JovemRESUMO
A subset of prostate cancer displays a poor clinical outcome. Therefore, identifying this poor prognostic subset within clinically aggressive groups (defined as a Gleason score (GS) â§8) and developing effective treatments are essential if we are to improve prostate cancer survival. Here, we performed a bioinformatics analysis of a TCGA dataset (GS â§8) to identify pathways upregulated in a prostate cancer cohort with short survival. When conducting bioinformatics analyses, the definition of factors such as "overexpression" and "shorter survival" is vital, as poor definition may lead to mis-estimations. To eliminate this possibility, we defined an expression cutoff value using an algorithm calculated by a Cox regression model, and the hazard ratio for each gene was set so as to identify genes whose expression levels were associated with shorter survival. Next, genes associated with shorter survival were entered into pathway analysis to identify pathways that were altered in a shorter survival cohort. We identified pathways involving upregulation of GRB2. Overexpression of GRB2 was linked to shorter survival in the TCGA dataset, a finding validated by histological examination of biopsy samples taken from the patients for diagnostic purposes. Thus, GRB2 is a novel biomarker that predicts shorter survival of patients with aggressive prostate cancer (GS â§8).
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Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Proteína Adaptadora GRB2/metabolismo , Neoplasias da Próstata/metabolismo , Adulto , Idoso , Estudos de Coortes , Proteína Adaptadora GRB2/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Neoplasias da Próstata/genética , Transdução de Sinais , Análise de Sobrevida , Regulação para Cima/genéticaRESUMO
BRCA1/2 mutation carriers are at high risk for type II ovarian, fallopian tube or peritoneal cancer. Although risk-reducing salpingo-oophorectomy plays an important role in the prevention of these BRCA1/2-associated gynecological cancers, occult ovarian, fallopian tube, or peritoneal cancer is discovered upon risk-reducing salpingo-oophorectomy in 1-4% of BRCA1/2 mutation carriers. Notably, around 30% of BRCA1/2 mutation carriers who undergo risk-reducing salpingo-oophorectomy have undergone adjuvant chemotherapy for breast cancer. We describe the discovery and treatment of occult cancer at the edge of the left fimbria in a BRCA1 mutation carrier who had, just a short time previously, undergone neoadjuvant paclitaxel plus carboplatin (TC) chemotherapy for triple-negative breast cancer. During subsequent risk-reducing salpingo-oophorectomy, a 5.5-mm nodule was observed at the edge of the left fimbria. Microscopic examination of the tumour tissue revealed high-grade serous carcinoma with degenerate tumour cells and fibrosis. Peritoneal fluid was negative for cancer cells. Two months later, hysterectomy, omentectomy and retroperitoneal lymphadenectomy were performed. The final diagnosis was stage FIGO IA fallopian tube cancer. Adjuvant chemotherapy (TC administered every 3 weeks) was applied, and there has been no evidence of recurrence for 5 years. In applying gynecologic surgery and adjuvant chemotherapy, we followed the general recommendation for stage IA fallopian tube cancer. There is no standard strategy for the treatment of occult fallopian tube cancer detected after chemotherapy for BRCA1-associated triple-negative breast cancer. According to our experience in this case, we believe the clinical value of staging laparotomy in cases of a small occult BRCA1/2-associated gynecological cancer should be further investigated.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/patologia , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/patologia , Salpingo-Ooforectomia , Carboplatina/uso terapêutico , Quimioterapia Adjuvante , Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/uso terapêuticoRESUMO
BACKGROUND: Primary epithelial ovarian cancer is divided into several subtypes. The relationships between apparent diffusion coefficient (ADC) values and their subtypes have not yet been established. PURPOSE: To investigate whether ADC values of epithelial ovarian cancer vary according to histologic tumor cellularity and evaluate the difference of clear cell carcinoma (CCC), high-grade serous carcinoma (HGSC), and endometrioid carcinoma (EC). MATERIAL AND METHODS: This retrospective study included 51 cases of epithelial ovarian cancer (17 CCC, 20 HGSC, and 14 EC) identified by magnetic resonance imaging with pathological confirmation. All patients underwent diffusion-weighted imaging and the ADC values of lesions were measured. We counted the tumor cells in three high-power fields and calculated the average for each case. The Spearman's correlation coefficient test was used to analyze correlation between ADC values and tumor cellularity. The ADC values of HGSC, EC, and CCC were compared using the Steel-Dwass test. RESULTS: The ADC values of all cases were significantly inversely correlated with tumor cellularity (rs = -0.761; P < 0.001). The mean ± SD ADC values (×10-3 mm2/s) of CCC, HGSC, and EC were 1.24 ± 0.17 (range 0.98--1.65), 0.84 ± 0.10 (range 0.67--1.06), and 0.84 ± 0.10 (range 0.67--1.07). The mean ± SD tumor cellularity of CCC, HGSC, and EC was 162.88 ± 63.28 (range 90.33--305.67), 440.60 ± 119.86 (range 204.67--655.67), and 461.02 ± 81.86 (range 333.33--602.33). CONCLUSION: There is a significant inverse correlation between ADC values and tumor cellularity in epithelial ovarian cancer. The mean ADC value of CCC was higher than those of HGSC and EC, seemingly due to the low cellularity of CCC.
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Adenocarcinoma de Células Claras/diagnóstico por imagem , Carcinoma Endometrioide/diagnóstico por imagem , Cistadenocarcinoma Seroso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/patologia , Estudos RetrospectivosRESUMO
Deep learning algorithms have been successfully used in medical image classification. In the next stage, the technology of acquiring explainable knowledge from medical images is highly desired. Here we show that deep learning algorithm enables automated acquisition of explainable features from diagnostic annotation-free histopathology images. We compare the prediction accuracy of prostate cancer recurrence using our algorithm-generated features with that of diagnosis by expert pathologists using established criteria on 13,188 whole-mount pathology images consisting of over 86 billion image patches. Our method not only reveals findings established by humans but also features that have not been recognized, showing higher accuracy than human in prognostic prediction. Combining both our algorithm-generated features and human-established criteria predicts the recurrence more accurately than using either method alone. We confirm robustness of our method using external validation datasets including 2276 pathology images. This study opens up fields of machine learning analysis for discovering uncharted knowledge.
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Processamento de Imagem Assistida por Computador , Conhecimento , Patologia , Algoritmos , Automação , Compressão de Dados , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Curva ROCRESUMO
Deep learning algorithms have achieved great success in cancer image classification. However, it is imperative to understand the differences between the deep learning and human approaches. Using an explainable model, we aimed to compare the deep learning-focused regions of magnetic resonance (MR) images with cancerous locations identified by radiologists and pathologists. First, 307 prostate MR images were classified using a well-established deep neural network without locational information of cancers. Subsequently, we assessed whether the deep learning-focused regions overlapped the radiologist-identified targets. Furthermore, pathologists provided histopathological diagnoses on 896 pathological images, and we compared the deep learning-focused regions with the genuine cancer locations through 3D reconstruction of pathological images. The area under the curve (AUC) for MR images classification was sufficiently high (AUC = 0.90, 95% confidence interval 0.87-0.94). Deep learning-focused regions overlapped radiologist-identified targets by 70.5% and pathologist-identified cancer locations by 72.1%. Lymphocyte aggregation and dilated prostatic ducts were observed in non-cancerous regions focused by deep learning. Deep learning algorithms can achieve highly accurate image classification without necessarily identifying radiological targets or cancer locations. Deep learning may find clues that can help a clinical diagnosis even if the cancer is not visible.
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Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Humanos , MasculinoRESUMO
Granular cell tumor (GCT) is a rare neoplasm of the soft tissues and <1% of all GCTs are malignant. Initially, GCT was considered a myogenic lesion affecting the female breast (myoblastoma). We report the case of an 83-year-old woman with a palpable lump in the left breast; mammography and ultrasound showed an irregular lesion. It was difficult to differentiate it from a malignant lesion; therefore, we performed core needle biopsy and histopathologic examination and immunohistochemical studies revealed a GCT of the breast.
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OBJECTIVES: The aim of this study was to use immunohistochemistry to differentiate solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia (IPUDH). Three types of high-molecular-weight cytokeratins (CKs) - CK5/6, CK14, and CK34betaE12 - were targeted. METHODS: We studied 17 patients with solid papillary carcinoma in situ and 18 patients with IPUDH diagnosed by at least two pathologists. Immunohistochemical analyses used antibodies to CK5/6, CK14, and CK34betaE12 to make the differential diagnosis of solid papillary carcinoma in situ versus IPUDH. Immunohistochemical staining was scored as 0-5 using Allred score. RESULTS: Immunohistochemistry with CK5/6 and CK14 antibodies produced scores of 0-3 in all patients with solid papillary carcinoma in situ and 2-5 in all patients with IPUDH. Immunohistochemical staining with CK34betaE12 antibody produced scores of 1-3 in all patients with solid papillary carcinoma and 3-5 in all patients with IPUDH. In tissues from patients with IPUDH, significantly more cells were stained with CK34betaE12 than CK5/6 (p < 0.05) or CK14 (p < 0.05). CONCLUSION: The immunoreactivity of CK5/6, CK14, and CK34betaE12 antibodies was useful to differentiate solid papillary carcinoma in situ from IPUDH. CK34betaE12 is especially useful for distinguishing solid papillary carcinoma from IPUDH.
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The agonistic/antagonistic biocharacter of selective estrogen receptor modulators (SERMs) can have therapeutic advantages, particularly in the case of premenopausal breast cancers. Although the contradictory effects of these modulators have been studied in terms of crosstalk between the estrogen receptor α (ER) and coactivator dynamics and growth factor signaling, the molecular basis of these mechanisms is still obscure. We identify a series of regulatory mechanisms controlling cofactor dynamics on ER and SERM function, whose activities require F-box protein 22 (Fbxo22). Skp1, Cullin1, F-box-containing complex (SCFFbxo22) ubiquitylated lysine demethylase 4B (KDM4B) complexed with tamoxifen-bound (TAM-bound) ER, whose degradation released steroid receptor coactivator (SRC) from ER. Depletion of Fbxo22 resulted in ER-dependent transcriptional activation via transactivation function 1 (AF1) function, even in the presence of SERMs. In living cells, TAM released SRC and KDM4B from ER in a Fbxo22-dependent manner. SRC release by TAM required Fbxo22 on almost all ER-SRC-bound enhancers and promoters. TAM failed to prevent the growth of Fbxo22-depleted, ER-positive breast cancers both in vitro and in vivo. Clinically, a low level of Fbxo22 in tumor tissues predicted a poorer outcome in ER-positive/human epidermal growth factor receptor type 2-negative (HER2-negative) breast cancers with high hazard ratios, independently of other markers such as Ki-67 and node status. We propose that the level of Fbxo22 in tumor tissues defines a new subclass of ER-positive breast cancers for which SCFFbxo22-mediated KDM4B degradation in patients can be a therapeutic target for the next generation of SERMs.
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Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteínas F-Box/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas de Neoplasias/metabolismo , Proteólise , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Proteínas F-Box/genética , Feminino , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Células MCF-7 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas de Neoplasias/genética , Receptores Citoplasmáticos e Nucleares/genética , Tamoxifeno/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: The purpose of this study was to evaluate the possible clinical application of optical coherence tomography for assessing ovarian reserve in individual specimens of human ovarian tissue for fertility preservation. METHODS: Ovarian tissue examination by optical coherence tomography was performed before ovarian tissue cryopreservation. Three of the four subjects had hematological disease or cancer, and they faced a threat to their fertility due to impending chemotherapy. One patient underwent ovarian tissue extraction for in vitro activation of dormant follicles as fertility treatment. RESULTS: The current full-field optical coherence tomography technique can detect primordial follicles in non-fixed and non-embedded human ovarian tissue. These images are well correlated with histological evaluation and the ovarian reserve test, including follicle counts. CONCLUSION: It was demonstrated that optical coherence tomography could assess localization of primordial follicles and ovarian reserve in specimens of non-fixed human ovarian cortex, although optimization for examination of human ovarian tissue is needed for clinical application. Additionally, this technique holds the possibility of assessing the ovarian reserve of patients with unevaluable ovarian reserve. TRIAL REGISTRATION NUMBER: UMIN000023141.
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Preservação da Fertilidade , Infertilidade Feminina/terapia , Folículo Ovariano/citologia , Ovário/citologia , Ovário/transplante , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Neoplasias do Ânus/fisiopatologia , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Reserva OvarianaRESUMO
Here, cases of a 68- (Case 1) and a 44-year-old (Case 2) female are presented. They had an abnormality in the breast, and came to our hospital for further examination and treatment. Radiologically, malignancy could not completely excluded so breast excision was performed. Histologically, both cases revealed papillary neoplastic lesions lined by fibrovascular core and nuclear inverse polarity without atypia. Loss of myoepithelial cells was observed by HE, p63, and calponin. Previous report indicate CK5/6, ER, p63 and MUC3 are important for distinguishing between papillary lesions according to the differential index (based on Allred score) of ([ER total score] + [MUC3 total score])/([CK5/6 total score] + [p63 total score] + 1). Based on this analysis, our two cases had benign lesions. However, based on immunopositivity for cell-cycle marker Cyclin-D1, Case 1 was negative, and Case 2 was about 70% positive. Additionally, the Ki-67 index was <1% in both cases, and no evidence of disease was observed after a maximum 62 months of follow-up in both cases, despite lack of additional treatment. Thus, we propose that lack of myoepithelial cells in papillary lesions do not necessarily indicate malignancy and are thought to be, at the most, uncertain malignant potential.