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1.
J Pathol Transl Med ; 55(6): 380-387, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34614346

RESUMO

BACKGROUND: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. METHODS: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). RESULTS: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. CONCLUSIONS: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

2.
Sci Rep ; 11(1): 20205, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642389

RESUMO

The purpose of this study is to investigate imaging characteristics of young age breast cancer (YABC) focusing on correlation with pathologic factors and association with disease recurrence. From January 2017 to December 2019, patients under 40 years old who were diagnosed as breast cancer were enrolled in this study. Morphologic analysis of tumor and multiple quantitative parameters were obtained from pre-treatment dynamic contrast enhanced breast magnetic resonance imaging (DCE-MRI). Tumor-stroma ratio (TSR), microvessel density (MVD) and endothelial Notch 1 (EC Notch 1) were investigated for correlation with imaging parameters. In addition, recurrence associated factors were assessed using both clinico-pathologic factors and imaging parameters. A total of 53 patients were enrolled. Several imaging parameters derived from apparent diffusion coefficient (ADC) histogram showed negative correlation with TSR; and there was negative correlation between MVD and Ve in perfusion analysis. There were nine cases of recurrences with median interval of 16 months. Triple negative subtype and low CD34 MVD positivity in Notch 1 hotspots showed significant association with tumor recurrence. Texture parameters reflecting tumor sphericity and homogeneity were also associated with disease recurrence. In conclusion, several quantitative MRI parameters can be used as imaging biomarkers for tumor microenvironment and can predict disease recurrence in YABC.

3.
Biomed Res Int ; 2021: 3898585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337008

RESUMO

Purpose: Capsular formation around breast implants can produce various complications, including erythema, tenderness, discomfort, and breast deformation. Moreover, the capsule is thought to be correlated with breast implant-associated anaplastic large cell lymphoma. The proposed technique of capsule reduction can prevent some of these complications. Thus, the authors suggest a no-touch technique in two-stage, implant-based breast reconstruction. Patients and Methods. This single-center retrospective study evaluated the medical records and digitalized pathological slides of patients who underwent two-stage, implant-based breast reconstruction between February 2018 and May 2019. The selected patients were divided into group A and group B. Group A underwent a no-touch technique that included the following two steps: (1) using a sizer as the frame to create the submuscular and acellular dermal matrix (ADM) pocket for expander insertion and (2) inserting the expander through the funnel. After the second stage of implant insertion, the capsule was harvested for biopsy of the ADM, chest wall, and muscle. Results: This study included 33 breasts (31 patients): 18 in group A and 15 in group B. The capsular thicknesses of the ADM, the chest wall, and the muscle of group A were significantly thinner than those in group B. Pearson's correlation coefficient indicated negative correlations between capsular thickness and age; underlying disease; lesion side; interval of two-stage implant insertion; size of the expander; and radiotherapy, chemotherapy, or hormone therapy. Conclusion: To reduce the incidence of capsular formation following breast reconstruction using prostheses, a no-touch technique that uses a funnel and sizer to avoid implant contact is both efficient and beneficial.


Assuntos
Implantes de Mama/efeitos adversos , Mamoplastia/efeitos adversos , Adulto , Biópsia , Mama/patologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Dispositivos para Expansão de Tecidos
4.
J Breast Cancer ; 24(2): 164-174, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33818022

RESUMO

PURPOSE: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. METHODS: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3-4, 5-6, and 7-8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. RESULTS: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8-96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. CONCLUSION: Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01069211.

5.
Sci Rep ; 11(1): 8154, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854094

RESUMO

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), APC (60%), and KRAS (49%). TP53 mutations were significantly linked to higher overall stage (p = 0.038) and lower disease-free survival (DFS) (p = 0.039). ATM mutation was significantly associated with higher tumor stage (p = 0.012) and shorter overall survival (OS) (p = 0.041). Stage 3 and 4 patients with ATM mutations (p = 0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p = 0.002). However, the OS of patients with or without TP53, RAS, APC, PIK3CA, and SMAD4 mutations did not differ significantly (p = 0.59, 0.72, 0.059, 0.25, and 0.12, respectively). Similarly, the DFS between patients with RAS, APC, PIK3CA, and SMAD4 mutations and those with wild-type were not statistically different (p = 0.3, 0.79, 0.13, and 0.59, respectively). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p = 0.043). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/cirurgia , Mutação , Análise de Sequência de DNA/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Análise de Sobrevida
6.
Front Oncol ; 11: 609743, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718163

RESUMO

Background: Yes-associated protein 1 (YAP1) is a transcription factor regulated by the Hippo pathway and functions as an oncogene in various solid tumors under dysregulated Hippo pathway. However, the role of YAP1 in breast cancer remains controversial. Here, we investigated the impact of different levels of nuclear YAP1 expression on the clinical characteristics and survival outcome in patients with breast cancer. Patients and Methods: Retrospectively obtained 455 breast tumor samples at Gangnam Severance Hospital were examined for YAP1 expression by immunohistochemistry, and the clinical data were analyzed. External validation was performed using a retrospective cohort and tissues in 482 patients from Severance Hospital. Results: High nuclear YAP1 expression was associated with hormone receptor negativity and aggressive tumor behavior, including lymph node metastasis, high Ki67 labeling index and inferior distant metastasis-free survival (DMFS, hazard ratio [HR] 2.271, 95% confidence intervals [CIs] 1.109-4.650, P = 0.0249), and also confirmed inferior disease free survival (HR 3.208, 95% CIs 1.313-7.833, P = 0.0105) in external validation cohort. In patients with triple-negative breast cancer (TNBC), high nuclear YAP1 expression was an independent significant determinant of poor DMFS (HR 2.384, 95% CIs 1.055-5.386, P = 0.0367). Conclusion: Our findings suggest that nuclear YAP1 expression is a biomarker of adverse prognosis and a potential therapeutic target in patients with breast cancer, especially in TNBC.

7.
J Breast Cancer ; 24(1): 1-21, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33634617

RESUMO

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

8.
J Pathol Transl Med ; 55(1): 1-15, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33461287

RESUMO

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

9.
PLoS One ; 15(11): e0241514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166334

RESUMO

Breast cancers with PIK3CA mutations can be treated with PIK3CA inhibitors in hormone receptor-positive HER2 negative subtypes. We applied a supervised elastic net penalized logistic regression model to predict PIK3CA mutations from gene expression data. This regression approach was applied to predict modeling using the TCGA pan-cancer dataset. Approximately 10,000 cases were available for PIK3CA mutation and mRNA expression data. In 10-fold cross-validation, the model with λ = 0.01 and α = 1.0 (ridge regression) showed the best performance, in terms of area under the receiver operating characteristic (AUROC). The final model was developed with selected hyper-parameters using the entire training set. The training set AUROC was 0.93, and the test set AUROC was 0.84. The area under the precision-recall (AUPR) of the training set was 0.66, and the test set AUPR was 0.39. Cancer types were the most important predictors. Both insulin like growth factor 1 receptor (IGF1R) and the phosphatase and tensin homolog (PTEN) were the most significant genes in gene expression predictors. Our study suggests that predicting genomic alterations using gene expression data is possible, with good outcomes.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Regulação Neoplásica da Expressão Gênica , Mutação/genética , Neoplasias/genética , Humanos , Modelos Genéticos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
10.
World J Gastroenterol ; 26(40): 6207-6223, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33177794

RESUMO

BACKGROUND: Identifying genetic mutations in cancer patients have been increasingly important because distinctive mutational patterns can be very informative to determine the optimal therapeutic strategy. Recent studies have shown that deep learning-based molecular cancer subtyping can be performed directly from the standard hematoxylin and eosin (H&E) sections in diverse tumors including colorectal cancers (CRCs). Since H&E-stained tissue slides are ubiquitously available, mutation prediction with the pathology images from cancers can be a time- and cost-effective complementary method for personalized treatment. AIM: To predict the frequently occurring actionable mutations from the H&E-stained CRC whole-slide images (WSIs) with deep learning-based classifiers. METHODS: A total of 629 CRC patients from The Cancer Genome Atlas (TCGA-COAD and TCGA-READ) and 142 CRC patients from Seoul St. Mary Hospital (SMH) were included. Based on the mutation frequency in TCGA and SMH datasets, we chose APC, KRAS, PIK3CA, SMAD4, and TP53 genes for the study. The classifiers were trained with 360 × 360 pixel patches of tissue images. The receiver operating characteristic (ROC) curves and area under the curves (AUCs) for all the classifiers were presented. RESULTS: The AUCs for ROC curves ranged from 0.693 to 0.809 for the TCGA frozen WSIs and from 0.645 to 0.783 for the TCGA formalin-fixed paraffin-embedded WSIs. The prediction performance can be enhanced with the expansion of datasets. When the classifiers were trained with both TCGA and SMH data, the prediction performance was improved. CONCLUSION: APC, KRAS, PIK3CA, SMAD4, and TP53 mutations can be predicted from H&E pathology images using deep learning-based classifiers, demonstrating the potential for deep learning-based mutation prediction in the CRC tissue slides.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Aprendizado Profundo , Neoplasias do Colo/genética , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética , Genes p53 , Humanos , Mutação
11.
Pathol Res Pract ; 216(5): 152835, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31983568

RESUMO

Development of molecular technology has led to the expansion of next generation sequencing (NGS) in area of diagnostic pathology. Here we present a case in which a lung tumor, which resembled an atypical carcinoid tumor, was revealed as metastatic breast cancer by next generation sequencing. A 50-year-old female, who had received modified radical mastectomy for breast cancer, presented with a 2.1 cm sized lung mass. The mass was well-defined, well-enhanced, and showed endobronchial component by computed tomography. Under the impression of carcinoid tumor, right upper lobectomy was performed. Tumor cells were immunohistochemically positive for chromogranin and CD56, but negative for cytokeratin 7 and GCDFP-15. Initially, the patient was diagnosed with atypical carcinoid tumor. However, subsequent NGS test revealed GATA3 mutation (p.Ala333fs) of the lung tumor. After a thorough review of literature and public cancer genome data about GATA3 mutation, the diagnosis was revised to metastatic invasive carcinoma from breast.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Tumor Carcinoide/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Neoplasias da Mama/genética , Diagnóstico Diferencial , Feminino , Fator de Transcrição GATA3/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Mutação
12.
J Pathol Transl Med ; 54(1): 87-94, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31718121

RESUMO

BACKGROUND: Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens. METHODS: This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary's Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0-8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers. RESULTS: In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively. CONCLUSIONS: CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

13.
Magn Reson Imaging ; 66: 36-41, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785544

RESUMO

PURPOSE: We aimed to investigate the magnetic resonance imaging (MRI) features and clinicopathologic factors with recurrence of triple-negative breast cancer (TNBC). PATIENTS AND METHODS: We identified 281 patients with 288 surgically confirmed TNBC lesions who underwent pretreatment MRI between 2009 and 2015. The presence of intratumoral high signal on T2-weighted images, high-signal rim on diffusion-weighted images (DWI), and rim enhancement on the dynamic contrast-enhanced MRI and clinicopathological data were collected. Cox proportional analysis was performed. RESULTS: Of the 288 lesions, 36 (12.5%) recurred after a median follow-up of 18 months (range, 3.6-68.3 months). Rim enhancement (hazard ratio [HR] = 3.15; 95% confidence interval [CI] = 1.01, 9.88; p = .048), and lymphovascular invasion (HR = 2.73, 95% CI = 1.20, 6.23; p = .016) were independently associated with disease recurrence. While fibroglandular volume, background parenchymal enhancement, intratumoral T2 high signal, and high-signal rim on DWI, were not found to be risk factors for recurrence. CONCLUSION: Pretreatment MRI features may help predict a high risk of recurrence in patients with TNBC.


Assuntos
Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Mama/patologia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Seguimentos , Humanos , Aumento da Imagem/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Adulto Jovem
14.
Pathol Res Pract ; 215(11): 152595, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31570282

RESUMO

INTRODUCTION: The detection of BRCA1/2 mutations is important because PARP1 inhibitors are approved for germline and/or somatic BRCA-mutated advanced ovarian cancer. Next-generation sequencing (NGS) is increasingly used in clinical practice for BRCA1/2 mutations. The purpose of this study was to consider several conditions of NGS BRCA1/2 assay applicable to clinical laboratory tests, in particular for using formalin fixed paraffin embedded (FFPE) ovarian tissues. MATERIALS AND METHODS: We selected 64 ovarian cancer patients and performed Oncomine™ BRCA assay using FFPE tissue. Effect of FFPE sample quality was analyzed by NGS quality parameters including deamination metric. Somatic variants were selected by removing germline variants of peripheral blood and interpreted as pathogenic, variants of unknown significance, and false positive. RESULTS: We found a positive relationship between the number of variants over the deamination metric and FFPE age (P < 0.001) with a cutoff values of approximately 0.7 and 60 months, respectively. When comparing NGS results with Sanger sequencing, NGS misreported 3 of 15 variants using default parameters which were corrected after changing parameters. We detected somatic variants in eight patients and classified them into pathogenic (n = 3), VUS (n = 3) and false positive (n = 2). CONCLUSIONS: This study is important for improving BRCA1/2 mutation detection capabilities of NGS analytical pipelines and strategy to overcome their limitations using FFPE tissue in ovarian cancer patients.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Ovarianas/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Feminino , Formaldeído , Humanos , Pessoa de Meia-Idade , Mutação , Inclusão em Parafina , República da Coreia , Fixação de Tecidos , Adulto Jovem
15.
Int J Med Sci ; 16(8): 1096-1101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523171

RESUMO

Objective: Efficient and highly predictive biomarkers reflecting the prognosis of persistent atypical squamous cells of unknown significance(ASCUS) and low grade squamous intraepithelial lesion(LSIL)s are unavailable and need to be developed urgently. We aimed to develop a predictive model for diagnosis of cervical intraepithelial neoplasia(CIN)2+ by analyzing the immunocytochemical expression of the HPV L1 capsid protein in patients with persistent ASCUS and LSIL with a high risk of HPV infection. Methods: Cervical cytology samples comprising (70 ASCUS and 215 LSIL Pap smears) were analyzed. Immunocytochemical identification of the HPV L1 capsid protein in cervical cytology samples was performed. Expression levels of HPV L1 capsid protein in cervical cytology samples were measured, and the correlation between HPV L1 expression and cervical pathologic diagnosis was evaluated. The risk for CIN2+ was calculated using the results of immunocytochemistry and the HPV DNA test. Results: Negative results for HPV L1 immunochemistry test were more frequently observed in CIN2+, and expression of the HPV L1 capsid protein was higher in CIN1 or cervicitis (Fisher's exact test, p<0.05). Diagnosis rates for CIN2+ were highest for the combination of HPV L1 capsid protein immunocytochemistry, cytology and HPV test when compared with other combinations (Akaike information criterion (AIC): 191.7, Schwarz criterion(SC): 206.3, p<0.001). Conclusion: Absence of HPV L1 capsid expression and presence of HPV type 16 or 18 infection are reliable predictors of progression to CIN2+ in patients showing persistent ASCUS and LSIL.


Assuntos
Células Escamosas Atípicas do Colo do Útero/virologia , Biomarcadores Tumorais/análise , Proteínas do Capsídeo/análise , Neoplasia Intraepitelial Cervical/virologia , Proteínas Oncogênicas Virais/análise , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Células Escamosas Atípicas do Colo do Útero/metabolismo , Células Escamosas Atípicas do Colo do Útero/patologia , Proteínas do Capsídeo/metabolismo , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Prognóstico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adulto Jovem
16.
J Clin Med ; 8(8)2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390831

RESUMO

Corneal dystrophies (CDs) are a diverse group of inherited disorders with a heterogeneous genetic background. Here, we report the identification of a novel ZNF143 heterozygous missense mutation in three individuals of the same family with clinical and pathological features that are consistent with endothelial CD. Ophthalmologic examination revealed diffuse corneal clouding and edema with decreased endothelial cell density. Pathological findings showed increased corneal thickness due to edema of basal epithelial cells and stroma, and abnormal metaplastic endothelium with stratified epithelium-like changes. Patients' metaplastic corneal endothelial cells expressed predominantly cytokerain 7, cytokeratin 19, and E-cadherin. Although Sanger sequencing did not detect any mutation associated with endothelial CDs, whole exome sequencing identified the ZNF143 c.937G>C p.(Asp313His) mutation as a candidate gene for our patients' endothelial CD. In-vitro functional studies demonstrated that mutant ZNF143 promoted the mesenchymal-to-epithelial transition; it upregulated the expression of genes associated with epithelialization in human corneal endothelial cells. Additionally, proinflammatory cytokine responsive genes were significantly enriched after mutant ZNF143 transfection, which may contribute to the severe phenotype of the three patients. These findings link a mutation in ZNF143 with endothelial CD for the first time.

17.
Breast Cancer Res Treat ; 176(1): 119-130, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30989460

RESUMO

PURPOSE: Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence. METHODS: Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-ß downstream pathway. RESULTS: miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGFßRII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGFßRII, especially in cells transfected with both miRNAs. CONCLUSION: miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-ß activity, leading to early breast cancer carcinogenesis.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , MicroRNAs/genética , Fator de Crescimento Transformador beta/metabolismo , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Interferência de RNA , Transdução de Sinais , Transcriptoma
18.
Yonsei Med J ; 60(2): 158-162, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30666837

RESUMO

PURPOSE: Trastuzumab is an effective treatment for human epidermal growth factor receptor 2 (HER2)-amplified breast cancers. We sought to develop a simple protocol for HER2 image analysis of breast cancer specimens. MATERIALS AND METHODS: In a preliminary test, we found that at least 1000 tumor cells need to be examined in the most strongly stained areas. Next, we evaluated the clinical usefulness of this established protocol of image analysis in 555 breast cancer patients. Results of the HER2 immunohistochemical (IHC) staining were compared between manual scoring and image analysis. RESULTS: The HER2 IHC results obtained by the image analysis method correlated well with those obtained by the manual scoring method (Cohen's kappa=0.830). Using the HER2 silver in situ hybridization (SISH) results as a gold standard, sensitivity values were 72.1% for manual scoring and 74.0% for image analysis; specificity values were 96.2% for manual scoring and 94.7% for image analysis; and accuracy values were 91.7% for manual scoring and 90.8% for image analysis. McNemar's test was applied to the results, and there were no statistically significant differences in sensitivity and specificity between the positive (p=0.688) and negative (p=0.118) SISH groups. CONCLUSION: HER2 image analysis results were similar to those obtained via the manual scoring method, indicating that the use of image analysis can reduce assessment time and effort. We suggest that image analysis-based evaluation of 1000 tumor cells in the most strongly IHC-stained area, regardless of stroma content, is sufficient for determining HER2 expression levels in breast cancer specimens.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Processamento de Imagem Assistida por Computador , Receptor ErbB-2/metabolismo , Coloração e Rotulagem , Adulto , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
19.
Int J Clin Exp Pathol ; 12(2): 664-668, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933872

RESUMO

BACKGROUND: Primary angiosarcoma of the breast is extremely rare, accounting for less than 0.05% of all primary malignancies of the breast. Here, we report here a case of primary angiosarcoma with full description of radiology and histology, including electron microscopic findings. CASE PRESENTATION: A 39-year-old woman complained of a diffuse hard mass in her right breast. She did not have any history of radiation exposure. Ultrasonography revealed a 7 cm sized mass with an irregular anechoic cystic portion replacing the entire right breast. Modified radical mastectomy was performed. The diagnosis of intermediate grade angiosarcoma was made by microscopic examination, immunohistochemical staining, and electron microscopic examination. The patient underwent four cycles of adriamycin-ifosfamide chemotherapy and received radiation therapy. Multiple bone metastases occurred 9 months after surgery and palliative treatment was given. Follow up was lost at post-operative 22 months. CONCLUSIONS: We report a rare case of intermediate grade primary angiosarcoma with detailed radiological and histological findings. Despite postoperative chemoradiation therapy, multiple metastases suggest that intermediate grade may have a more aggressive behavior.

20.
J Breast Cancer ; 22(4): 562-578, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31897330

RESUMO

Purpose: Triple-negative breast cancer (TNBC) is associated with poor prognosis with limited treatment options. Angiogenesis is known to be involved in the progression of TNBC, and targeting this pathway results in modest clinical benefits. In this study, we analyzed the role of tumor microvascular endothelial Notch1 (EC Notch1) and tumoral miR-34a as prognostic markers in patients with TNBC. Methods: The expression of miR-34a was analyzed using archival tumor tissues from 114 patients with TNBC. Simultaneously, archival tumor tissues were also checked for the expression of CD34 and Notch1 by immunostaining. The ratio of Notch1-microvascular density (MVD) to CD34-MVD was defined as EC Notch1. The association between the expression of miR-34a or EC Notch1 and clinicopathological characteristics was analyzed. Results: In the overall patient population, patients with low expression of EC Notch1 was associated with better overall survival (OS, p = 0.041) than those with high expression of EC Notch1. In lymph node-positive TNBC patients, high levels of miR-34a and low levels of EC Notch1 correlated significantly with higher survival benefits in terms of OS (p = 0.026), disease-free survival (p = 0.009), and metastasis-free survival (p = 0.038) relative to that in other patients. Decreased expression of EC Notch1 and increased expression of miR-34a also showed a survival benefit in locally advanced TNBC. Conclusion: The fact that miR-34a and EC Notch1 are associated with the angiogenesis suggests that angiogenesis may play a role in the development and progression of TNBC.

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