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Our study aimed to analyze five monovarietal honeys from the Salah Eddine region in Iraq, focusing on physicochemical, antioxidant, and antimicrobial properties and polyphenolic compounds. Our objective was to evaluate the strengths and qualities of Iraqi honeys, ensuring compliance with the Codex Alimentarius standard for honey. The spectrophotometric analysis included assessments of reduced sugar (75.8-77.7%), fructose-to-glucose ratio (0.7-0.9%), sucrose (2.2-2.9%), HMF (17.23-18.87 mg/kg), and melanoidin content (0.25-0.44), which were all determined. The electrical conductivity (0.39-0.46 mS/cm) using a conductivity meter, pH (4.02-4.31), and mineral composition were determined in all samples using atomic absorption spectrometry. Antioxidant activities were spectrophotometrically determined, through DPPH free radical scavenging (7.87-95.62 mg/mL), as was the total antioxidant activity (14.26-22.15 mg AAE/g), with correlations established with biochemical constituents such as the total phenol content, highlighting the significant presence of Coumaric acid (0.38-2.34 µg/mL), Catechin (1.80-2.68 µg/mL), and Quercetin (0.30 µg/mL) using HPLC. The study also observed notable antimicrobial activities using Escherichia coli, Staphylococcus aureus, and Candida albicans on Mueller-Hinton agar as well as through diffusion technique. In conclusion, our findings, including the antioxidant and antimicrobial strengths, underscore the substantial potential of Iraqi honeys in mitigating damage and preventing the onset of various diseases, affirming their good quality and adherence to international honey standards.
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Antiinfecciosos , Miel , Miel/análisis , Antioxidantes/química , Irak , Minerales/análisisRESUMEN
The US Food and Drug Administration (FDA) approved the PD-L1 immunohistochemical assay, SP142, as a companion test to determine eligibility for atezolizumab therapy in patients with advanced triple negative breast cancer (TNBC) but data in lung cancer studies suggest the assay suffers from poor reproducibility. We sought to evaluate reproducibility and concordance in PD-L1 scoring across multiple pathologists. Full TNBC sections were stained with SP142 and SP263 assays and interpreted for percentage (%) immune cell (IC) staining by 19 pathologists from 14 academic institutions. Proportion of PD-L1 positive cases (defined as ≥1% IC) was determined for each assay as well as concordance across observers. We utilized a new method we call Observers Needed to Evaluate Subjective Tests (ONEST) to determine the minimum number of evaluators needed to estimate concordance between large numbers of readers, as occurs in the real-world setting. PD-L1 was interpreted as positive with the SP142 assay in an average 58% of cases compared with 78% with SP263 (p < 0.0001). IC positive continuous scores ranged from 1 to 95% (mean = 20%) and 1 to 90% (mean = 10%) for SP263 and SP142, respectively. With SP142, 26 cases (38%) showed complete two category (<1% vs. ≥1%) concordance; with SP263, 38 cases (50%) showed complete agreement. The intraclass correlation coefficient (ICC) for two category scoring of SP263 and SP142 was 0.513 and 0.560. ONEST plots showed decreasing overall percent agreement (OPA) as observer number increased, reaching a low plateau of 0.46 at ten observers for SP263 and 0.41 at eight observers for SP142. IC scoring with both assays showed poor reproducibility across multiple pathologists with ONEST analysis suggesting more than half of pathologists will disagree about IC scores. This could lead to many patients either receiving atezolizumab when they are unlikely to benefit, or not receiving atezolizumab when they may benefit.
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Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Inmunohistoquímica , Neoplasias de la Mama Triple Negativas/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Femenino , Humanos , Selección de Paciente , Estudios Prospectivos , Reproducibilidad de los Resultados , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer. METHODS: Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed. Immunohistochemistry with double staining for MAGI2 and p63 was performed and analyzed by image analysis as percent of analyzed area (%AREA). Multivariable logistic regression was used to correlate MAGI2 expression with clinical outcomes. Generalized Estimating Equations (GEE) with linear and logistic regression was used to correlate MAGI2 with intrapatient histology. RESULTS: MAGI2 %AREA was inversely associated with progression from HGPIN to adenocarcinoma of low to high Gleason score (OR, 0.980; slope, -0.02; P = 0.005) and HGPIN to cancer of any Gleason score (OR, 0.969; P = 0.007). After adjusting for grade, stage, and margin status, MAGI2 %AREA was a significant independent predictor of biochemical recurrence (BCR) (OR, 0.936; 95%CI, 0.880-0.996; P = 0.037; bootstrap P = 0.017). The addition of MAGI2 %AREA to these standard clinical parameters improved accuracy of predicting BCR by 2.9% (91.0% vs 88.1%). CONCLUSIONS: These results reveal that MAGI2 expression is reduced during prostate cancer progression and that retention of MAGI2 signal reduces odds of BCR. The study results further suggest a possible role of MAGI2 in prostate neoplasia. Decreased MAGI2 expression may help predict prostate cancer aggressiveness and provide new insight for treatment decisions and post-operative surveillance intervals.
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Adenocarcinoma/genética , Proteínas Portadoras/genética , Recurrencia Local de Neoplasia/genética , Neoplasias de la Próstata/genética , Proteínas Adaptadoras Transductoras de Señales , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adenocarcinoma/terapia , Anciano , Progresión de la Enfermedad , Expresión Génica , Guanilato-Quinasas , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapiaRESUMEN
The introduction of Prostate Specific Antigen (PSA) screening has caused a stage shift in diagnosis of prostate cancer and an increasing number of patients receiving early diagnosis. This has led to early detection of limited foci of cancer on prostate biopsy, and clinically insignificant prostate cancer at radical prostatectomy. Therefore, current methods for sampling, diagnosing and managing prostate cancer have significantly evolved in recent years. In light of recent management changes and conservative surveillance protocols prompting new handling, grading and staging guidelines, the evaluation of prostate biopsy in contemporary practice has become pivotal. It is therefore critical to recognize minor foci of cancer or atypical glands, and distinguish these from benign mimics that could lead to a false positive diagnosis.In this chapter, current biopsy modalities and imaging techniques, tissue handling and recent updates in the interpretation of prostate biopsy will be discussed.
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Biopsia con Aguja , Neoplasias de la Próstata/diagnóstico , Humanos , Masculino , Estadificación de Neoplasias , Antígeno Prostático Específico , ProstatectomíaRESUMEN
Author affiliations in chapter 4 was incorrect and it has now been corrected in this version.
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PURPOSE: Fine needle aspiration with and without concurrent core needle biopsy is a minimally invasive method to diagnose and assist in management of renal masses. We assessed the pathological accuracy of fine needle aspiration compared to and associated with core needle biopsy and the impact on management. MATERIALS AND METHODS: We performed a single institution, retrospective study of 342 cases from 2001 to 2015 with small and large renal masses (4 or less and greater than 4 cm, respectively). Diagnostic and concordance rates, and the impact on management were analyzed. RESULTS: Adequacy rates for fine needle aspiration only, core needle biopsy only and fine needle aspiration plus core needle biopsy were 21%, 12% and 8% (aspiration vs aspiration plus biopsy p <0.026). In the aspiration plus biopsy group adding aspiration to biopsy and biopsy to aspiration reduced the inadequacy rate from 23% to 8% and from 27% to 8% for a total reduction rate of 15% and 19%, respectively, corresponding to 32 cases (9.3%). Rapid on-site examination contributed to a 22.5% improvement in fine needle aspiration adequacy rates. In this cohort 30% of aspiration only, 5% of biopsy only and 12% of aspiration plus biopsy could not be subtyped (aspiration vs biopsy p <0.0001, aspiration vs aspiration plus biopsy p <0.0127 and biopsy vs aspiration plus biopsy p = 0.06). The diagnostic concordance rate with surgical resection was 99%. Conversion of an inadequate specimen to an adequate one by a concurrent procedure impacted treatment in at least 29 of 32 patients. Limitations include the retrospective design and accuracy measurement based on surgical intervention. CONCLUSIONS: Fine needle aspiration plus core needle biopsy vs at least fine needle aspiration alone may improve diagnostic yield when sampling renal masses but it has subtyping potential similar to that of core needle biopsy only.
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Biopsia con Aguja Fina , Biopsia con Aguja Gruesa , Neoplasias Renales/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
The diagnosis of minimal prostatic adenocarcinoma can be challenging on prostate needle biopsy, and immunohistochemistry may be used to support the diagnosis of cancer. The International Society of Urologic Pathology currently recommends the use of the basal cell markers high-molecular-weight cytokeraratin and p63, and α-methylacyl-coenzyme-A racemase. However, there are caveats associated with the interpretation of these markers, particularly with benign mimickers. Another issue is that of early detection of presence and progression of disease and prediction of recurrence after clinical intervention. There remains a lack of reliable biomarkers to accurately predict low-risk cancer and avoid over treatment. As such, aggressive forms of prostate cancer may be missed and indolent disease may be subjected to unnecessary radical therapy. New biomarker discovery promises to improve early detection and prognosis and to provide targets for therapeutic interventions. In this review, we present the emerging immunohistochemical biomarkers of prostate cancer PTEN, ERG, FASN, MAGI-2, and SPINK1, and address their diagnostic and prognostic advantages and limitations.
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Biomarcadores de Tumor/análisis , Neoplasias de la Próstata/diagnóstico , Humanos , Inmunohistoquímica , Masculino , Pronóstico , Neoplasias de la Próstata/química , Neoplasias de la Próstata/mortalidadRESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation is associated with prostatic enlargement and resistance to 5α-reductase inhibitor (5ARI) therapy. Activation of the nuclear factor-kappa B (NF-κB) pathway is linked to both inflammation and ligand-independent prostate cancer progression. METHODS: NF-κB activation and androgen receptor variant (AR-V) expression were quantified in transition zone tissue samples from patients with a wide range of AUASS from incidental BPH in patients treated for low grade, localized peripheral zone prostate cancer to advanced disease requiring surgical intervention. To further investigate these pathways, human prostatic stromal and epithelial cell lines were transduced with constitutively active or kinase dead forms of IKK2 to regulate canonical NF-κB activity. The effects on AR full length (AR-FL) and androgen-independent AR-V expression as well as cellular growth and differentiation were assessed. RESULTS: Canonical NF-κB signaling was found to be upregulated in late versus early stage BPH, and to be strongly associated with non-insulin dependent diabetes mellitus. Elevated expression of AR-variant 7 (AR-V7), but not other AR variants, was found in advanced BPH samples. Expression of AR-V7 significantly correlated with the patient AUASS and TRUS volume. Forced activation of canonical NF-κB in human prostatic epithelial and stromal cells resulted in elevated expression of both AR-FL and AR-V7, with concomitant ligand-independent activation of AR reporters. Activation of NF-κB and over expression of AR-V7 in human prostatic epithelial cells maintained cell viability in the face of 5ARI treatment. CONCLUSION: Activation of NF-κB and AR-V7 in the prostate is associated with increased disease severity. AR-V7 expression is inducible in human prostate cells by forced activation of NF-κB resulting in resistance to 5ARI treatment, suggesting a potential mechanism by which patients may become resistant to 5ARI therapy.
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FN-kappa B/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Receptores Androgénicos/metabolismo , Anciano , Línea Celular Tumoral , Supervivencia Celular/genética , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Próstata/patología , Hiperplasia Prostática/genética , Hiperplasia Prostática/patología , Receptores Androgénicos/genética , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is treated with 5α-reductase inhibitors (5ARI). These drugs inhibit the conversion of testosterone to dihydrotestosterone resulting in apoptosis and prostate shrinkage. Most patients initially respond to 5ARIs; however, failure is common especially in inflamed prostates, and often results in surgery. This communication examines a link between activation of NF-κB and increased expression of SRD5A2 as a potential mechanism by which patients fail 5ARI therapy. METHODS: Tissue was collected from "Surgical" patients, treated specifically for lower urinary tract symptoms secondary to advanced BPH; and, cancer free transition zone from "Incidental" patients treated for low grade, localized peripheral zone prostate cancer. Clinical, molecular and histopathological profiles were analyzed. Human prostatic stromal and epithelial cell lines were genetically modified to regulate NF-κB activity, androgen receptor (AR) full length (AR-FL), and AR variant 7 (AR-V7) expression. RESULTS: SRD5A2 is upregulated in advanced BPH. SRD5A2 was significantly associated with prostate volume determined by Transrectal Ultrasound (TRUS), and with more severe lower urinary tract symptoms (LUTS) determined by American Urological Association Symptom Score (AUASS). Synthesis of androgens was seen in cells in which NF-κB was activated. AR-FL and AR-V7 expression increased SRD5A2 expression while forced activation of NF-κB increased all three SRD5A isoforms. Knockdown of SRD5A2 in the epithelial cells resulted in significant reduction in proliferation, AR target gene expression, and response to testosterone (T). In tissue recombinants, canonical NF-κB activation in prostatic epithelium elevated all three SRD5A isoforms and resulted in in vivo growth under castrated conditions. CONCLUSION: Increased BPH severity in patients correlates with SRD5A2 expression. We demonstrate that NF-κB and AR-V7 upregulate SRD5A expression providing a mechanism to explain failure of 5ARI therapy in BPH patients. Prostate 76:1004-1018, 2016. © 2016 Wiley Periodicals, Inc.
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3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Resistencia a Medicamentos , FN-kappa B/fisiología , Hiperplasia Prostática/tratamiento farmacológico , Receptores Androgénicos/fisiología , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/fisiología , Animales , Apoptosis , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Isoenzimas/genética , Isoenzimas/fisiología , Síntomas del Sistema Urinario Inferior/patología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Ratones , Ratones Desnudos , FN-kappa B/antagonistas & inhibidores , Orquiectomía , Próstata/patología , Hiperplasia Prostática/patología , Hiperplasia Prostática/cirugía , Neoplasias de la Próstata Resistentes a la Castración , Testosterona/biosíntesis , Insuficiencia del Tratamiento , Regulación hacia ArribaRESUMEN
The utility of routine frozen section (FS) analysis for margin evaluation during radical prostatectomy (RP) remains controversial. A retrospective search was conducted to identify RPs evaluated by FS over a 5-year period. The potential of FS to discriminate between benign and malignant tissue and to predict final margins was evaluated. During the study period, 71 (12.3%) of 575 cases underwent FS evaluation of margins, generating 192 individual FSs. There were 8 FSs diagnosed as atypical/indeterminate because of significant freezing, crushing, and/or thermal artifacts; 11 as positive for carcinoma; and 173 as benign. Two FSs classified as benign were diagnosed as positive for carcinoma on subsequent permanent section. Frozen sections' sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis of prostatic adenocarcinoma were 85%, 100%, 100%, 99%, and 99%, respectively. Overall RP final margin predictive accuracy was 81%. Positive FS was significantly associated with perineural invasion on biopsy and extraprostatic extension and higher stage disease on RP, but not with the overall final margin status. The high FS accuracy supports its use to guide the extent of surgery. However, FS cannot be used to predict the overall final margin status. Recognition of the histological artifacts inherent to the FS procedure is important to ensure appropriate utilization.
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Carcinoma/patología , Secciones por Congelación , Próstata/patología , Prostatectomía , Neoplasias de la Próstata/patología , Vesículas Seminales/patología , Biopsia , Carcinoma/diagnóstico , Humanos , Masculino , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico , Estudios RetrospectivosRESUMEN
PURPOSE: There have been conflicting data in studies on the prognostic role of high risk human papillomavirus in penile squamous cell carcinoma. Using P16(ink4a) over expression as a surrogate marker for high risk human papillomavirus, we evaluated high risk human papillomavirus status with respect to various clinical features, including recurrence and overall survival, among others. MATERIALS AND METHODS: P16(ink4a) over expression was evaluated by immunohistochemistry for 119 consecutive patients with penile squamous cell carcinoma. Several variables were recorded including age, stage, histological grade, lymph node status, lymphovascular invasion, metastasis and recurrence. Median followup was 30 months. RESULTS: P16(ink4a) over expression was detected in 49.5% (59 of 119) of samples. There was no significant difference between P16(ink4a) negative and P16(ink4a) positive tumors in terms of stage (p = 0.518), histological grade (p = 0.225), lymphovascular invasion (p = 0.388), overall survival (p = 0.156) or lymph node metastasis (p = 0.748). P16(ink4a) negative tumors were more likely to recur overall (p = 0.04), especially if patients had positive lymph nodes at diagnosis (p = 0.002). CONCLUSIONS: These data suggest that P16(ink4a)/high risk human papillomavirus status is associated with recurrence, especially in patients with positive lymph nodes at diagnosis. Thus, patients with P16(ink4a) negative penile cancer, particularly those with lymph node metastases, may warrant closer observation after surgery.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirugía , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia/genética , Neoplasias del Pene/genética , Neoplasias del Pene/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/secundario , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias del Pene/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Approximately one-third of patients fail medical treatment for benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) requiring surgical intervention. Our purpose was to establish a molecular characterization for patients undergoing surgical intervention for LUTS to address therapeutic deficiencies. METHODS: Clinical, molecular, and histopathological profiles were analyzed in 26 patients undergoing surgery for severe LUTS. Incidental transitional zone nodules were isolated from 37 patients with mild symptoms undergoing radical prostatectomy. Clinical parameters including age, prostate volume, medication, prostate specific antigen, symptom score, body mass index, and incidence of diabetes were collected. Multivariate logistic regression analysis with adjustments for potential confounding variables was used to examine associations between patient clinical characteristics and molecular targets identified through molecular profiling. RESULTS: Compared to incidental BPH, progressive symptomatic BPH was associated with increased expression of the activating protein-1 transcription factor/chemokine network. As expected, inverse correlations were drawn between androgen receptor levels and age, as well as between 5α-reductase inhibitor (5ARI) treatment and tissue prostate specific antigen levels; however, a novel association was also drawn between 5ARI treatment and increased c-FOS expression. CONCLUSIONS: This study provides molecular evidence that a network of pro-inflammatory activating protein-1 transcription factors and associated chemokines are highly enriched in symptomatic prostate disease, a profile that molecularly categorizes with many other chronic autoimmune diseases. Because 5ARI treatment was associated with increased c-FOS expression, future studies should explore whether increased activating protein-1 proteins are causal factors in the development of symptomatic prostate disease, inflammation or resistance to traditional hormonal therapy.
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Síntomas del Sistema Urinario Inferior/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/genética , Factor de Transcripción AP-1/genética , Anciano , Humanos , Síntomas del Sistema Urinario Inferior/genética , Síntomas del Sistema Urinario Inferior/cirugía , Masculino , Persona de Mediana Edad , Próstata/cirugía , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/cirugía , Factor de Transcripción AP-1/metabolismoRESUMEN
The homeodomain-containing transcription factor, NKX3.1, plays an important role in the suppression of prostate tumorigenesis. Herein, we identify the receptor activity-modifying protein 1 (RAMP1) as a direct NKX3.1 target gene through analysis of chromatin immunoprecipitation coupled to massively parallel sequencing and gene expression data. RAMP1 is a coreceptor for certain G-protein-coupled receptors, such as the calcitonin gene-related peptide receptor, to the plasma membrane. We found that RAMP1 expression is specifically elevated in human prostate cancer relative to other tumor types. Furthermore, RAMP1 mRNA and protein levels are significantly higher in human prostate cancer compared with benign glands. We identified multiple NKX3.1 binding sites in the RAMP1 locus in human prostate cancer cells and in the normal mouse prostate. Analyses of Nkx3.1 knockout mice and human prostate cancer cell lines indicate that NKX3.1 represses RAMP1 expression. Knockdown of RAMP1 by shRNA decreased prostate cancer cell proliferation and tumorigenicity in vitro and in vivo. By using gene expression profiling and pathway analyses, we identified several cancer-related pathways that are significantly altered in RAMP1 knockdown cells, including the mitogen-activated protein kinase signaling pathway. Further experiments confirmed a reduction in MAP2KI (MEK1) expression and phosphorylated-extracellular signal-regulated kinase 1/2 levels in RAMP1 knockdown cells. These data provide novel insights into the role of RAMP1 in promoting prostate tumorigenesis and support the potential of RAMP1 as a novel biomarker and possible therapeutic target in prostate cancer.
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Carcinogénesis/patología , Proteínas de Homeodominio/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteína 1 Modificadora de la Actividad de Receptores/genética , Factores de Transcripción/metabolismo , Regulación hacia Arriba/genética , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Genes Relacionados con las Neoplasias , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Desnudos , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/enzimología , Unión Proteica/genética , Proteína 1 Modificadora de la Actividad de Receptores/metabolismoRESUMEN
This study aimed to assess the diagnostic value of vimentin expression in differentiating endometrioid adenocarcinoma of primary uterine corpus and ovarian origin. Immunohistochemical analyses for the expression of vimentin in tumoral epithelial cells were performed on 149 endometrioid adenocarcinomas wherein the primary sites were not in question, including whole tissue sections of 27 carcinomas of uterine corpus origin (and no synchronous ovarian tumor), 7 carcinomas of ovarian origin (and no synchronous uterine corpus tumor) and a tissue microarray (TMA) containing 91 primary uterine corpus and 24 primary ovarian carcinomas. We also assessed 15 cases that synchronously involved the uterine corpus and ovary, 15 cases of metastasis to organs/tissues other than uterine corpus or ovary as well as 7 lymph node metastases. Vimentin was negative in 97% (30/31) of primary ovarian carcinomas. In contrast, 82% (97/118) of primary uterine corpus carcinomas were vimentin-positive. Vimentin expression was discordant in 53% of synchronous tumors. The sensitivity and specificity of negative vimentin staining in predicting an ovarian primary were 97% and 82%, respectively, whereas parallel values for positive vimentin staining in predicting a primary uterine tumor were 82% and 97%, respectively. The pattern of vimentin expression in all cases was maintained in their respective regional lymph nodes and distant metastases. In conclusion, ovarian and uterine corpus endometrioid adenocarcinomas have different patterns of vimentin expression. If validated in larger and/or different data sets, these findings may have diagnostic value in distinguishing metastatic lesions from double primary tumors involving both sites.
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Biomarcadores de Tumor/metabolismo , Carcinoma Endometrioide/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Neoplasias Uterinas/patología , Vimentina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
An antibody cocktail directed against p63, cytokeratin (CK)5/14, and CK7/18 is reported to be useful in distinguishing noninvasive from invasive breast lesions and for the characterization of intraductal epithelial proliferations. However, limited studies evaluate its use in clinical practice. A retrospective review of breast material at a university medical center identified cases that were immunostained with the above antibody cocktail. Additional p63 immunostaining alone was performed to further determine the utility of the antibody cocktail in the evaluation of invasion. Of 50 breast cases identified, the antibody cocktail was used to confirm or exclude invasion in 44 (88%). Twenty-two (50%) of these had easily identifiable p63/CK5/14-positive myoepithelial cells, whereas the remainder lacked such staining, confirming the diagnosis of invasive carcinoma. In 27 cases with available diagnostic material for additional p63 immunostaining, the cocktail better highlighted myoepithelial cells by staining nuclei and cytoplasm. Easier identification of invasion was also facilitated by CK7/18 expression in invasive foci, especially those composed of single cells. Ten cases were immunostained to help determine the nature of an intraductal proliferation. The cocktail demonstrated a mosaic staining pattern of both CK7/18- and CK5/14-positive epithelial cells in 3 (30%) cases consistent with usual hyperplasia; homogenous CK7/18 expression in the remaining cases supported the diagnosis of atypical ductal hyperplasia or carcinoma in situ. In summary, the p63/CK7/18/CK5/14 cocktail stain appears to be a useful tool in diagnostic breast pathology, in the evaluation of possible invasion, particularly in the setting of minute foci of invasion as well as in epithelial proliferations.
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Anticuerpos Antineoplásicos , Neoplasias de la Mama/diagnóstico , Queratinas/inmunología , Factores de Transcripción/inmunología , Proteínas Supresoras de Tumor/inmunología , Biopsia con Aguja , Neoplasias de la Mama/patología , Femenino , Humanos , Queratina-14/análisis , Queratina-14/inmunología , Queratina-18/análisis , Queratina-18/inmunología , Queratina-5/análisis , Queratina-5/inmunología , Queratina-7/análisis , Queratina-7/inmunología , Queratinas/análisis , Invasividad Neoplásica , Estudios Retrospectivos , Factores de Transcripción/análisis , Proteínas Supresoras de Tumor/análisisRESUMEN
The gallbladder (GB) is a susceptible organ, prone to various pathologies that can be identified using different imaging techniques. Transabdominal ultrasound (TUS) is typically the initial diagnostic method due to its numerous well-established advantages. However, in cases of uncertainty or when a definitive diagnosis cannot be established, computed tomography (CT) or magnetic resonance imaging may be employed to provide more detailed information. Nevertheless, CT scans may sometimes offer inadequate spatial resolution, which can limit the differentiation of GB lesions, particularly when smaller yet clinically relevant abnormalities are involved. Conversely, endoscopic ultrasound (EUS) provides higher frequency compared to TUS, superior spatial resolution, and the option for contrast-enhanced harmonic imaging, enabling a more comprehensive examination. Thus, EUS can serve as a supplementary tool when conventional imaging methods are insufficient. This review will describe the standard EUS examination of the GB, focusing on its endosonographic characteristics in various GB pathologies.
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Background and Aims: Ulcerative colitis (UC) and Crohn's disease (CD) are the most common types of Inflammatory bowel disease (IBD), with variable responses to traditional therapies and unpredicted prognosis. In Egypt and most developing countries, the lack of recent epidemiological and prognostic data adversely affects management strategies. We collected and analyzed data of patients with IBD from multiple centers across Egypt to evaluate patients' clinical and epidemiological characteristics. Methods: This retrospective multicenter study included patients diagnosed with IBD between May 2018 and August 2021, at 14 tertiary gastroenterology units across Egypt. Record analysis addressed a combination of clinico-epidemiological characteristics, biochemical tests, stool markers, endoscopic features, histological information, and different lines for IBD treatment. Results: We identified 1104 patients with an established diagnosis of IBD; 81% of them had UC, and 19% showed CD. The mean age of onset was 35.1 ± 12.5 years ranging from 5 to 88 years, the mean duration of illness at inclusion was 13.6 ± 16.7 years, gender distribution was almost equal with a significant male dominance (60.4%, p = 0.003) among patients with CD, 57% were living in rural areas, and 70.5% were from Delta and Coastal areas. Two hundred nineteen patients (19.8%) displayed comorbid conditions, primarily associated with CD. The most frequent complaints were diarrhea (73.2%), rectal bleeding (54.6%) that was significantly higher among patients with UC (64%, p < 0.001), and 46.8% with abdominal pain (more often with CD: 71%, p < 0.001). Conventional therapy was effective in treating 94.7% of patients. The main lesion in patients with CD was ileal (47.8%); patients with UC mainly exhibited proctosigmoiditis (28.4%). Dysplasia was detected in 7.2% of patients, mainly subjects with UC. Conclusions: To our knowledge, our effort is the first and largest cohort of Egyptian patients with IBD to describe clinical and epidemiological characteristics, and diagnostic and management approaches. More extensive prospective studies are still needed to fully characterize disease distribution, environmental factors, and pathological features of the disease.
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Luminal cytokeratin (CK) expression in breast papillary lesions, and its potential diagnostic utility among other markers in distinguishing between papillomas and papillary carcinomas, has not been previously evaluated. Such expression was determined in 42 papillary lesions (18 papillary carcinomas and 24 papillomas) by immunostaining with a CK5/p63/CK8/18 antibody cocktail. The mean CK8/18 intensity score and percentage of positive cells were significantly higher in papillary carcinomas (227 and 95%, respectively, vs 86 and 42% in papillomas; both P-values <0.0001), whereas the mean CK5 intensity score and percentage of positive cells were significantly lower (7 and 5%, respectively, vs 107 and 58% in papillomas; both P-values <0.0001). Half (9/18) of the papillary carcinomas expressed p63 vs all (24/24) of the papillomas (P = 0.0001). P63 expression in papillary carcinoma was always (9/9; 100%) focal/limited in nature (expression in <10% of cells), whereas focal expression was seen in only four (17%) papillomas (P<0.0001). Both differential CK (CK8/18 and CK5) expression and p63 were equally sensitive (100%) for the diagnosis of papillary carcinoma, but differential CK expression was more specific (96 vs 83%), resulting in a greater accuracy. However, the best discriminatory power in the distinction from papilloma was achieved when all three markers were used in combination, resulting in 100% sensitivity and specificity values. It is concluded that breast papillary lesions have differential CK expression profiles that, especially in combination with p63, can be useful for their stratification, potentially also in needle biopsy material, in which more accurate and reproducible characterization is needed.
Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma Papilar/metabolismo , Inmunohistoquímica/métodos , Queratinas/metabolismo , Proteínas de la Membrana/metabolismo , Papiloma/metabolismo , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Carcinoma Papilar/química , Carcinoma Papilar/patología , Diagnóstico Diferencial , Femenino , Humanos , Queratinas/análisis , Proteínas de la Membrana/análisis , Papiloma/química , Papiloma/patología , Sensibilidad y EspecificidadRESUMEN
Breast carcinoma (BC) is one of the most common osteotropic tumors. The subset of BC patients with isolated bone metastasis (IBM) forms a clinically distinct group and often has a favorable clinical outcome as compared to others with metastatic BC. We analyzed all BC patients with distal organ metastasis in our institution between 1997 and 2003 (N = 198) to identify the clinicopathologic features of BC with IBM and compare them to those with metastasis to other sites. We found that 63% of BC patients with advanced disease had bone metastases, and 44% of those were IBM. The proportion of cases with IBM that expressed estrogen receptor and/or progesterone receptor (47/52; 90%) was significantly higher than those with non-bone metastases (P < .0001) and than those with multiple metastases involving bone (P < .0001). The distribution of BC molecular subtypes in cases of IBM was again significantly different from that of the remainder. By univariate and multivariate analysis of the clinicopathologic factors examined, only estrogen receptor and progesterone receptor status of the primary tumor was predictive for IBM. The median survival after diagnosis of metastatic disease was significantly longer in cases with IBM than that of any other group. Our results indicate that the diversity in receptor expression patterns not only reflects the biological diversity of mammary tumors but may also predict their metastatic potential and thus could potentially be used in surveying women patients with nonmetastatic disease.
Asunto(s)
Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/secundario , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Neoplasias Óseas/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Femenino , Hormonas/metabolismo , Humanos , Metástasis Linfática , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Adulto JovenRESUMEN
Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.