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1.
Urology ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711982

RESUMO

OBJECTIVE: To study if prostatic ductal adenocarcinoma (PDA) controlled by Grade Group (GG), PSA, and tumor volume (TV) is an independent predictor of adverse radical prostatectomy (RP) outcomes. MATERIALS: One-hundred-and-twenty-eight PDA and 1,141 acinar continuous RPs were studied. Each tumor nodule (TN) was individually graded, staged, and its TV measured. Univariate analysis (UVA) identified features associated with lymph node metastasis (LN+), extraprostatic extension (EPE), positive surgical margins (SM+), and seminal vesicle invasion (SV+). We then assessed PDA effect on RP outcomes in a multivariate analysis (MVA). RESULTS: In 127 cases PDA was present in 1 TN and no TN was pure PDA. One-hundred-and-twenty-three cases had PDA in TNs with highest grade, stage, and TV. Patients with PDA were older (65 vs. 63 years, p<0.001), had higher GG (p<0.001), and LN+ (6.3% vs 2.7%, p=0.049). Controlling these variables by GG eliminated statistical significance. Overall, there were 3,249 separate TNs (129 PDA and 3,120 acinar). In UVA, PDA predicted EPE (92/124 vs 517/3,045), SV+ (28/1129 vs 116/3,120), and SM+ (51/129 vs 296/3,120), all p<0.001. In MVA, PDA lost its effect on EPE (OR=0.88, p=0.64), SM+ (OR=0.86, p=0.5), and SV+ (OR=0.99, p=0.98). CONCLUSION: Controlled for grade and TV, PDA was not an independent predictor of adverse RP outcomes, but former two were. Hence, higher GG and TV associated with PDA TNs may be predictive of adverse RP outcomes rather than PDA by itself. These conclusions may be used in preoperative risk stratification and definitive therapy planning when PDA is identified on needle biopsy.

2.
Am J Clin Pathol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769792

RESUMO

OBJECTIVES: We aimed to determine the interobserver reproducibility in diagnosing low-grade ductal carcinoma in situ (DCIS). We also aimed to compare the interobserver variability using a proposed two-tiered grading system as opposed to the current three-tiered system. METHODS: Three expert breast pathologists and one junior pathologist identified low-grade DCIS from a set of 300 DCIS slides. Months later, participants were asked to grade the 300 cases using the standard three-tiered system. RESULTS: Using the two-tiered system, interobserver agreement among breast pathologists was considered moderate (κ = 0.575). The agreement was similar (κ = 0.532) with the junior pathologist included. Using the three-tiered system, pathologists' agreement was poor (κ = 0.235). CONCLUSIONS: Pathologists' reproducibility on diagnosing low-grade DCIS showed moderate agreement. Experience does not seem to influence reproducibility. Our proposed two-tiered system of low vs nonlow grade, where the intermediate grade is grouped in the nonlow category has shown improved concordance.

3.
Virchows Arch ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444626

RESUMO

Renal cell tumors with mixed morphology resembling multiple renal cell carcinoma (RCC) subtypes are generally regarded as unclassified RCC. However, occasionally, papillary adenoma or RCC appears admixed with a larger, different tumor histology. We retrieved 17 renal tumors containing a papillary adenoma or papillary RCC component admixed with another tumor histology and studied them with immunohistochemistry and fluorescence in situ hybridization (FISH). Larger tumors were oncocytomas (n = 10), chromophobe RCCs (n = 5), borderline oncocytic tumor (n = 1), and clear cell RCC (n = 1). The size of papillary component ranged from 1 to 34 mm. One tumor was an oncocytoma encircled by a cyst (2.0 cm) with papillary hyperplasia of the lining. The papillary lesions were diffusely cytokeratin 7 positive (17/17), in contrast to "host" tumors. Alpha-methylacyl-coA-racemase labeling was usually stronger in the papillary lesions (13/15). KIT was negative in all papillary lesions and the clear cell RCC and positive in 16/16 oncocytic or chromophobe tumors. Eight of 15 (53%) collision tumors had differing FISH results in the two components. A papillary renal cell proliferation within another tumor is an uncommon phenomenon with predilection for oncocytoma and chromophobe RCC, possibly related to their common entrapment of benign tubules. When supported by distinct morphology and immunohistochemistry in these two components, this phenomenon should be diagnosed as a collision of two processes. A diagnosis of unclassified RCC should be avoided, due to potential misrepresentation as an aggressive renal cancer.

4.
Prostate Int ; 7(1): 15-18, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30937293

RESUMO

Background: In recent years, anatomic pathology laboratories have been struck by new revenue policies secondary to the Affordable Care Act. In particular, modifications to compensation for processing prostatic core needle biopsies (PCNBs) have led to important reimbursement cuts. Herein, we explore a hypothetical reduction in the costs for the processing of PCNBs using three simple, hypothetical methods while maintaining high-standard patient care. Materials and methods: We determined the number of blocks and slides used per case on all PCNBs performed at our institution from August 2013 to September 2014 and calculated the total procedural cost for each case and for the total number of cases processed during the study period based on a published estimated procedural cost. We then estimated the procedural cost of three different proposed hypothetical scenarios that consisted in reducing the number of blocks used per case. A Student t test was used to assess the difference between real and hypothetical costs. Results: A total of 4,406 paraffin blocks were used to process 363 PCNBs with a total annual procedural cost of $26,303. By implementing any of the hypothetical scenarios, the annual procedural cost was significantly reduced; the reduction could potentially be as low as $8,978 (P < 0.0001). Conclusions: This study illustrates three hypothetical alternatives that could dramatically reduce the procedural costs of PCNBs while maintaining high-quality care. Implementation of these scenarios at a global scale could potentially have an impact on health-care cost in the USA of several millions of dollars per year.

5.
Biochem Biophys Res Commun ; 508(2): 536-542, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30509497

RESUMO

WNT/ß-catenin signaling plays pivotal roles in mammary development and tumorigenesis; and aberrant activation of this pathway is frequently observed in human breast cancer, correlating with poor outcome. However, the mechanisms underlying WNT-driven mammary tumorigenesis remain incompletely understood. Here, we used mouse mammary tumor virus (MMTV)-Wnt1 transgenic mice, which develop aggressive mammary adenocarcinomas, to examine whether Limb-Bud-and-Heart (LBH) - a WNT/ß-catenin target transcription co-factor overexpressed in human triple-negative breast cancers with WNT pathway hyperactivation, contributes to WNT-induced tumorigenesis. We found LBH is specifically overexpressed in basal epithelial tumor cells of MMTV-Wnt1 mammary tumors reminiscent of its basal cell-restricted expression in the normal postnatal mammary gland. To determine the role of LBH in mammary tumorigenesis, we crossed MMTV-Wnt1 mice with basal epithelial-specific Keratin 14/K14-Cre;LbhloxP knockout mice. Mammary glands from virgin LBH-deficient MMTV-Wnt1 mice exhibited reduced hyperplasia, cell proliferation and increased apoptosis. Importantly, LBH inactivation in mammary epithelium significantly delayed tumor onset in MMTV-Wnt1 transgenic mice, with a median tumor-free survival of 32.5 weeks compared to 22.5 weeks in control LBH wild type MMTV-Wnt1 mice (p < 0.05). This data provides the first evidence that LBH plays an essential role in WNT-induced mammary tumorigenesis by promoting hyperplastic growth and tumor formation.


Assuntos
Carcinogênese/induzido quimicamente , Hiperplasia/prevenção & controle , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/prevenção & controle , Proteínas Nucleares/deficiência , Animais , Proteínas de Ciclo Celular , Feminino , Vírus do Tumor Mamário do Camundongo/genética , Camundongos , Camundongos Transgênicos , Proteína Wnt1/genética
6.
Am J Surg Pathol ; 43(3): 369-373, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30557174

RESUMO

Our objective was to identify the best of the existing definitions of Gleason score (GS) at a positive surgical margin (PSM) by validating them in our radical prostatectomy cohort. We analyzed 251 patients who had mixed (3+4, 3+5, 4+3 or 5+3) pathologic GS and PSM. We used 5 definitions to record GS at a PSM. Univariate and multivariate analyses were used to study the association between each definition and the risk of biochemical recurrence (BCR). We also tested the prognostic value of multivariate models including established predictors and each of the studied definitions of GS at a PSM. GS 3+3 was seen at a PSM in 57.4% of the cases and was more common in patients with lower overall GS. Over a median follow-up of 4.0 years 89 patients (35.5%) developed BCR. All of the definitions of GS at a PSM were independent predictors of the BCR-free survival. Most of them also improved the prognostic value of the multivariate models when added to the established parameters. The degree of improvement was similar for the most complex definition (full GS at a PSM) and the easiest to record binary definition (presence of Gleason 4/5 pattern at a PSM). We conclude that compared with the other possible options of reporting GS at a PSM, the presence of Gleason 4/5 pattern may be the most practical definition. It is at least as predictive as other definitions, may be the easiest to record and is the best studied of the existing alternatives.

7.
Am J Clin Pathol ; 151(5): 479-485, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30576407

RESUMO

OBJECTIVES: Rete testis invasion by germ cell tumors is frequently concomitant with lymphovascular or spermatic cord invasion (LVI/SCI); independent implications for staging are uncertain. METHODS: In total, 171 seminomas and 178 nonseminomatous germ cell tumors (NSGCTs; 46 had 1%-60% seminoma component) came from five institutions. Metastatic status at presentation, as a proxy for severity, was available for all; relapse data were unavailable for 152. Rete direct invasion (ReteD) and rete pagetoid spread (ReteP) were assessed. RESULTS: ReteP and ReteD were more frequent in seminoma than NSGCT. In seminoma, tumor size bifurcated at 3 cm or more or less than 3 cm predicted metastatic status. Tumors with ReteP or ReteD did not differ in size from those without invasions but were less than with LVI/SCI; metastatic status or relapse did not show differences. In NSGCT, ReteP/ReteD did not correlate with size, metastatic status, or relapse. CONCLUSIONS: Findings support retaining American Joint Committee for Cancer pathologic T1 stage designation for rete testis invasion and pT1a/pT1b substaging of seminoma.

8.
Oncogene ; 38(6): 838-851, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30177837

RESUMO

Most prostate cancer cases remain indolent for long periods of time, but metastatic progression quickly worsens the prognosis and leads to mortality. However, little is known about what promotes the metastasis of prostate cancer and there is a lack of effective prognostic indicators, making it immensely difficult to manage options for treatment or surveillance. Arginyltransferase 1 (Ate1) is the enzyme mediating post-translational protein arginylation, which has recently been identified as a master regulator affecting many cancer-relevant pathways including stress response, cell cycle checkpoints, and cell migration/adhesion. However, the precise role of Ate1 in cancer remains unknown. In this study, we found the occurrence of metastasis of prostate cancer is inversely correlated with the levels of Ate1 protein and mRNA in the primary tumor. We also found that metastatic prostate cancer cell lines have a reduced level of Ate1 protein compared to non-metastatic cell lines, and that a depletion of Ate1 drives prostate cancer cells towards more aggressive pro-metastatic phenotypes without affecting proliferation rates. Furthermore, we demonstrated that a reduction of Ate1 can result from chronic stress, and that shRNA-reduced Ate1 increases cellular resistance to stress, and drives spontaneous and stress-induced genomic mutations. Finally, by using a prostate orthotropic xenograft mouse model, we found that a reduction of Ate1 was sufficient to enhance the metastatic phenotypes of prostate cancer cell line PC-3 in vivo. Our study revealed a novel role of Ate1 in suppressing prostate cancer metastasis, which has a profound significance for establishing metastatic indicators for prostate cancer, and for finding potential treatments to prevent its metastasis.


Assuntos
Aminoaciltransferases/metabolismo , Movimento Celular , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/metabolismo , Aminoaciltransferases/genética , Animais , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Knockout , Metástase Neoplásica , Proteínas de Neoplasias/genética , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia
9.
Surg Pathol Clin ; 11(3): 611-631, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30190144

RESUMO

Tissue sampling of renal masses is traditionally performed using percutaneous sonographic or CT guidance core biopsy (CB) with or without touch preparation cytology and/or fine-needle aspiration cytology (FNAC). The combined used of CB and FNAC is expanding in clinical practice, especially in small renal masses and plays a pivotal role in therapeutic decision making. Grouping the renal neoplasms in differential diagnostic groups helps in choosing specific immunohistochemical markers and reaching an accurate diagnosis.


Assuntos
Citogenética/métodos , Imuno-Histoquímica/métodos , Neoplasias Renais/patologia , Rim/citologia , Adulto , Biópsia por Agulha Fina , Diagnóstico Diferencial , Humanos , Sensibilidade e Especificidade
10.
Hum Pathol ; 78: 144-150, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29723604

RESUMO

Frozen section telepathology interpretation experience has been largely limited to practices with locations significantly distant from one another with sporadic need for frozen section diagnosis. In 2010, we established a real-time nonrobotic telepathology system in a very active cancer center for daily frozen section service. Herein, we evaluate its accuracy compared to direct microscopic interpretation performed in the main hospital by the same faculty and its cost-efficiency over a 1-year period. From 643 (1,416 parts) cases requiring intraoperative consultation, 333 cases (690 parts) were examined by telepathology and 310 cases (726 parts) by direct microscopy. Corresponding discrepancy rates were 2.6% (18 cases: 6 [0.9%] sampling and 12 [1.7%] diagnostic errors) and 3.2% (23 cases: 8 [1.1%] sampling and 15 [2.1%] diagnostic errors), P = .63. The sensitivity and specificity of intraoperative frozen diagnosis were 0.92 and 0.99, respectively, in telepathology and 0.90 and 0.99, respectively, in direct microscopy. There was no correlation of error incidence with postgraduate year level of residents involved in the telepathology service. Cost analysis indicated that the time saved by telepathology was $19,691.00 over 1 year of the study period, whereas the capital cost for establishing the system was $8,924.00. Thus, real-time nonrobotic telepathology is a reliable and easy-to-use tool for frozen section evaluation in busy clinical settings, especially when frozen section service involves more than one hospital, and it is cost-efficient when travel is a component of the service.


Assuntos
Erros de Diagnóstico , Secções Congeladas , Sensibilidade e Especificidade , Telepatologia , Docentes , Secções Congeladas/métodos , Humanos , Microscopia/métodos , Encaminhamento e Consulta , Telepatologia/métodos , Universidades
11.
J Am Soc Cytopathol ; 7(2): 79-85, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31043256

RESUMO

INTRODUCTION: Encapsulated follicular variant of papillary thyroid carcinoma (PTC) has an indolent behavior; hence, a change in terminology to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" has been proposed. Data are scant on the fine-needle aspiration (FNA) diagnosis of nodules proven to be NIFTP upon resection. The aim was to evaluate the FNA diagnosis of nodules diagnosed as NIFTP upon resection. MATERIALS AND METHODS: The archives of 8 participating institutions were searched for thyroid resection specimens obtained in a 1-year period, and pertinent demographic and pathology data were recorded. RESULTS: 2226 thyroid surgeries were performed over the indicated time period. NIFTP was diagnosed in 6.3% of cases; 118 patients (119 nodules) with NIFTP and available preoperative thyroid FNA were included. Preoperative cytologic diagnosis were: non-diagnostic: 0.8%; benign: 5.9%; atypia of undetermined significance/follicular lesion of undetermined significance: 42.9%; follicular neoplasm/suspicious for a follicular neoplasm: 31.0%; suspicious for malignancy: 15.9%; malignant: 3.4%. Molecular data was available for 49 cases, either by Afirma or ThyGenX/ThyroSeq. Of the Afirma cases, 11% were classified as "benign", 2% as "indeterminate", and 87% as "suspicious"; of the ThyGenX/ThyroSeq cases, 50% had NRAS mutations, 20% demonstrated KRAS mutations, 20% showed HRAS mutations, and 10% showed a BRAF mutation (K601E). CONCLUSIONS: NIFTP are tumors demonstrating nuclear features similar to those seen in PTC. Our series shows that a preoperative diagnosis of "suspicious for malignancy" or "malignant" is uncommon in NIFTP, suggesting that there are sufficient cytomorphologic differences between PTC and NIFTP to allow for the suspicion of NIFTP on FNA specimens.

12.
Nat Commun ; 8(1): 1204, 2017 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-29089489

RESUMO

Androgen deprivation (AD) therapy failure leads to terminal and incurable castration-resistant prostate cancer (CRPC). We show that the redox-protective protein thioredoxin-1 (TRX1) increases with prostate cancer progression and in androgen-deprived CRPC cells, suggesting that CRPC possesses an enhanced dependency on TRX1. TRX1 inhibition via shRNA or a phase I-approved inhibitor, PX-12 (untested in prostate cancer), impedes the growth of CRPC cells to a greater extent than their androgen-dependent counterparts. TRX1 inhibition elevates reactive oxygen species (ROS), p53 levels and cell death in androgen-deprived CRPC cells. Unexpectedly, TRX1 inhibition also elevates androgen receptor (AR) levels under AD, and AR depletion mitigates both TRX1 inhibition-mediated ROS production and cell death, suggesting that AD-resistant AR expression in CRPC induces redox vulnerability. In vivo TRX1 inhibition via shRNA or PX-12 reverses the castration-resistant phenotype of CRPC cells, significantly inhibiting tumor formation under systemic AD. Thus, TRX1 is an actionable CRPC therapeutic target through its protection against AR-induced redox stress.


Assuntos
Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Tiorredoxinas/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Dissulfetos/farmacologia , Humanos , Imidazóis/farmacologia , Masculino , Espécies Reativas de Oxigênio/metabolismo
13.
Reumatol. clín. (Barc.) ; 13(5): 252-257, sept.-oct. 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-165222

RESUMO

Objetivo. Realizar una amplia caracterización clínica y epidemiológica de nuestra población afectada de fibromialgia. Pacientes, material y método. Estudio observacional a lo largo de 2 años realizado en 3 centros de atención primaria de Terrassa. Muestra de 235 personas diagnosticadas de fibromialgia visitadas en consultas de atención primaria o de reumatología a las que se ofrece la asistencia al programa multidisciplinar y aceptan completar los datos iniciales del programa. Las mediciones principales fueron: datos sociodemográficos; hábitos tóxicos y ejercicio físico; comorbilidades; tratamientos para la fibromialgia; cuestionario de impacto de la fibromialgia (FIQ); escala hospitalaria de ansiedad-depresión (HADS), y cuestionario de funcionalidad familiar (APGAR familiar). Principales resultados. El 97,8% son mujeres; edad media, 54,6 años. Predominio de pacientes con estudios primarios y en situación de baja laboral. El 94% tienen comorbilidad asociada y solo el 3% no consumen ningún fármaco para su patología, a la vez que hay un elevado consumo de fármacos sin evidencia de efectividad en la fibromialgia. La mayoría puntúan como nivel moderado en el cuestionario de Impacto de la fibromialgia (FIQ); tienen patología ansiosa y/o depresiva probable en el 63 y el 53%, respectivamente, según la Escala hospitalaria de ansiedad y depresión (HADS) y soporte familiar correcto en el 62%, según el test APGAR familiar. Conclusiones. Se confirman como datos principales y coincidiendo con la bibliografía la gran prevalencia de la fibromialgia en mujeres, con elevada comorbilidad especialmente psiquiátrica-psicológica, con moderado impacto de la enfermedad y con importante consumo de fármacos sin eficacia demostrada (AU)


Objective. To perform an extensive clinical and epidemiological characterization of our fibromyalgia patients. Patients, material, and method. Two-year observational study in 3 primary care centers in Terrassa, Spain. We recruited a sample of 235 individuals diagnosed with fibromyalgia being treated in primary care or rheumatology clinics who, when offered inclusion in a multidisciplinary program, agreed to provide the initial data we requested. The main measures were sociodemographic data, unhealthy habits and physical activity, comorbidities, treatment for fibromyalgia, Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and a family functioning scale (family APGAR). Main results. In all, 97.8% were women and the average age was 54.6 years. Most of the patients had a primary school education and the majority was on sick leave. Ninety-four percent had associated comorbidity and only 3% were not taking any medication for their disease. Many were taking drugs with no proven efficacy in fibromyalgia. The majority had intermediate scores on the FIQ, the HADS showed that 63% and 53% had an anxious and/or probable depressive disorder, respectively, and, according to the family APGAR score, 62% received proper family support. Conclusions. In agreement with the literature, the major findings in our fibromyalgia patients were a marked predominance of women, a high incidence of comorbidities-mainly psychiatric disorders-a moderate impact of the disease and widespread use of drugs with no demonstrated efficacy (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fibromialgia/epidemiologia , Fibromialgia/prevenção & controle , Atenção Primária à Saúde/estatística & dados numéricos , Escala de Ansiedade Manifesta , Comorbidade , Exercício/fisiologia , Inquéritos e Questionários , Índice de Apgar , Estudos Transversais/métodos , Tratamento Farmacológico/classificação
14.
Case Rep Endocrinol ; 2017: 6734695, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29318061

RESUMO

The adrenal glands produce a variety of hormones that play a key role in the regulation of blood pressure, electrolyte homeostasis, metabolism, immune system suppression, and the body's physiologic response to stress. Adrenal neoplasms can be asymptomatic or can overproduce certain hormones that lead to different clinical manifestations. Oncocytic adrenal neoplasms are infrequent tumors that arise from cells in the adrenal cortex and display a characteristic increase in the number of cytoplasmic mitochondria. Since the rate-limiting step in steroidogenesis includes the transport of cholesterol across the mitochondrial membranes, in part carried out by the 18-kDa translocator protein (TSPO), we assessed the expression of TSPO in a case of adrenal oncocytic neoplasm using residual adrenal gland of the patient as internal control. We observed a significant loss of TSPO immunofluorescence expression in the adrenal oncocytic tumor cells when compared to adjacent normal adrenal tissue. We further confirmed this finding by employing Western blot analysis to semiquantify TSPO expression in tumor and normal adrenal cells. Our findings could suggest a potential role of TSPO in the tumorigenesis of this case of adrenocortical oncocytic neoplasm.

15.
Virchows Arch ; 470(1): 47-54, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27743032

RESUMO

Small cell-like change (SCLC) is a rare prostate lesion which has been described in only two previous studies (total of eight cases). Its relation to possible neuroendocrine differentiation remained unclear. We evaluated 11 SCLC cases with immunohistochemistry and electron microscopy. SCLC was characterized by crowded hyperchromatic small nuclei with scant cytoplasm, rosette-like structures, finely granular chromatin with indistinct nucleoli, and lack of mitoses, apoptoses, and necroses. In nine cases, SCLC was admixed with high-grade cancer, and in two cases, it represented a separate intraductal process, spatially remote from a low-volume Gleason score 6 (grade group 1) cancer. Only 2/11 SCLC labeled for synaptophysin, chromogranin, and serotonin, although 6/11 were at least focally positive for TTF1. Staining for NKX3.1 and pancytokeratin was typically weak, focal, and markedly reduced compared to the adjacent cancer. SCLC was positive for ERG in 1/8 and for racemase in 6/10 cases, again typically in a focal and weak fashion. There was no immunoreactivity with CD56, p63, or HMWCK. Ki-67 highlighted only rare nuclei (<1 %). No neuroendocrine granules were demonstrated by electron microscopy in four cases that showed no immunoreactivity for neuroendocrine markers. In summary, SCLC is more frequently found in high-grade prostate cancer, but it may also be encountered as a noninvasive lesion in Gleason score 6 (grade group 1) cancer. Importantly, it does not appear to indicate neuroendocrine differentiation. The low-grade cytology, the lack of mitoses and apoptoses, and the minimal Ki-67 reactivity are findings to support its discrimination from a small cell carcinoma.


Assuntos
Neoplasias da Próstata/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Pequenas/química , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Proliferação de Células , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/química , Neoplasias da Próstata/diagnóstico
16.
Reumatol Clin ; 13(5): 252-257, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27373583

RESUMO

OBJECTIVE: To perform an extensive clinical and epidemiological characterization of our fibromyalgia patients. PATIENTS, MATERIAL, AND METHOD: Two-year observational study in 3 primary care centers in Terrassa, Spain. We recruited a sample of 235 individuals diagnosed with fibromyalgia being treated in primary care or rheumatology clinics who, when offered inclusion in a multidisciplinary program, agreed to provide the initial data we requested. The main measures were sociodemographic data, unhealthy habits and physical activity, comorbidities, treatment for fibromyalgia, Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and a family functioning scale (family APGAR). MAIN RESULTS: In all, 97.8% were women and the average age was 54.6 years. Most of the patients had a primary school education and the majority was on sick leave. Ninety-four percent had associated comorbidity and only 3% were not taking any medication for their disease. Many were taking drugs with no proven efficacy in fibromyalgia. The majority had intermediate scores on the FIQ, the HADS showed that 63% and 53% had an anxious and/or probable depressive disorder, respectively, and, according to the family APGAR score, 62% received proper family support. CONCLUSIONS: In agreement with the literature, the major findings in our fibromyalgia patients were a marked predominance of women, a high incidence of comorbidities-mainly psychiatric disorders-a moderate impact of the disease and widespread use of drugs with no demonstrated efficacy.


Assuntos
Fibromialgia , Atenção Primária à Saúde , Adulto , Idoso , Comorbidade , Estudos Transversais , Feminino , Fibromialgia/diagnóstico , Fibromialgia/epidemiologia , Fibromialgia/psicologia , Fibromialgia/terapia , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espanha/epidemiologia
17.
Dev Cell ; 39(2): 155-168, 2016 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-27720612

RESUMO

The amyloid state of protein organization is typically associated with debilitating human neuropathies and is seldom observed in physiology. Here, we uncover a systemic program that leverages the amyloidogenic propensity of proteins to regulate cell adaptation to stressors. On stimulus, cells assemble the amyloid bodies (A-bodies), nuclear foci containing heterogeneous proteins with amyloid-like biophysical properties. A discrete peptidic sequence, termed the amyloid-converting motif (ACM), is capable of targeting proteins to the A-bodies by interacting with ribosomal intergenic noncoding RNA (rIGSRNA). The pathological ß-amyloid peptide, involved in Alzheimer's disease, displays ACM-like activity and undergoes stimuli-mediated amyloidogenesis in vivo. Upon signal termination, elements of the heat-shock chaperone pathway disaggregate the A-bodies. Physiological amyloidogenesis enables cells to store large quantities of proteins and enter a dormant state in response to stressors. We suggest that cells have evolved a post-translational pathway that rapidly and reversibly converts native-fold proteins to an amyloid-like solid phase.


Assuntos
Adaptação Fisiológica , Amiloide/metabolismo , Estresse Fisiológico , Motivos de Aminoácidos , Peptídeos beta-Amiloides/metabolismo , Animais , Fenômenos Biofísicos , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Feminino , Resposta ao Choque Térmico , Humanos , Células MCF-7 , Camundongos Nus , Chaperonas Moleculares/metabolismo , RNA não Traduzido/genética , Ribossomos/metabolismo
18.
Oncotarget ; 7(33): 53362-53376, 2016 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-27438142

RESUMO

Standard clinicopathological variables are inadequate for optimal management of prostate cancer patients. While genomic classifiers have improved patient risk classification, the multifocality and heterogeneity of prostate cancer can confound pre-treatment assessment. The objective was to investigate the association of multiparametric (mp)MRI quantitative features with prostate cancer risk gene expression profiles in mpMRI-guided biopsies tissues.Global gene expression profiles were generated from 17 mpMRI-directed diagnostic prostate biopsies using an Affimetrix platform. Spatially distinct imaging areas ('habitats') were identified on MRI/3D-Ultrasound fusion. Radiomic features were extracted from biopsy regions and normal appearing tissues. We correlated 49 radiomic features with three clinically available gene signatures associated with adverse outcome. The signatures contain genes that are over-expressed in aggressive prostate cancers and genes that are under-expressed in aggressive prostate cancers. There were significant correlations between these genes and quantitative imaging features, indicating the presence of prostate cancer prognostic signal in the radiomic features. Strong associations were also found between the radiomic features and significantly expressed genes. Gene ontology analysis identified specific radiomic features associated with immune/inflammatory response, metabolism, cell and biological adhesion. To our knowledge, this is the first study to correlate radiogenomic parameters with prostate cancer in men with MRI-guided biopsy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Imagem por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos
19.
J Urol ; 196(4): 1076-81, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27265220

RESUMO

PURPOSE: ISUP (International Society for Urologic Pathology) and WHO adopted prognostic Grade Groups 1 to 5 that simplify prostate cancer grading for prognosis. Grade Group 4 is Gleason score 8 cancer, which is heterogeneous, and it encompasses Gleason score 4 + 4 = 8, 3 + 5 = 8 and 5 + 3 = 8. The comparative prognostic implications of these various Gleason scores had not been studied by urological pathologists after a re-review of slides. MATERIALS AND METHODS: Patients with a highest biopsy Gleason score of 3 + 5 = 8 or 4 + 4 = 8 were included in the study. Controls were cases with a highest Gleason score of 4 + 3 = 7 or 9-10. A total of 423 prostatic biopsy cases accessioned from 2005 to 2013 at 2 institutions were reviewed. Clinicopathological findings and followup (median 33.4 months) were assessed. RESULTS: Among Gleason score 8 cancers the cancer status outcome in 51 men with Gleason score 3 + 5 = 8 was marginally worse than in 114 with Gleason score 4 + 4 = 8 (p = 0.04). This was driven by a persistent nonmetastatic (after radiation/hormone therapy) cancer rate of 37% among Gleason score 3 + 5 = 8 cases vs 24% among Gleason score 4 + 4 = 8 cases. Conversely, cancer specific survival at 36-month followup was 97.8% in 3 + 5 cases vs 92.6% in 4 + 4 cases but this was not significant (p = 0.089). Cancer specific survival in the Gleason score 8 group was dichotomized by the presence of cribriform growth (p = 0.018). All Gleason score categories did not differ in the fraction of biopsy cores positive, clinical presentation or pathological findings, including the frequency of Gleason pattern 5, in 70 patients who underwent prostatectomy. CONCLUSIONS: Using the most current standards of prostate cancer grading the prognosis is not different in Gleason score 3 + 5 = 8 and 4 + 4 = 8 cancers. This justifies including both in Grade Group 4.


Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Gradação de Tumores/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
20.
Breast Cancer Res Treat ; 158(1): 113-126, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27283835

RESUMO

Racial disparities in breast cancer incidence and outcome are a major health care challenge. Patients in the black race group more likely present with an early onset and more aggressive disease. The occurrence of high numbers of macrophages is associated with tumor progression and poor prognosis in solid malignancies. Macrophages are observed in adipose tissues surrounding dead adipocytes in "crown-like structures" (CLS). Here we investigated whether the numbers of CD163+ tumor-associated macrophages (TAMs) and/or CD163+ CLS are associated with patient survival and whether there are significant differences across blacks, non-black Latinas, and Caucasians. Our findings confirm that race is statistically significantly associated with the numbers of TAMs and CLS in breast cancer, and demonstrate that the highest numbers of CD163+ TAM/CLS are found in black breast cancer patients. Our results reveal that the density of CD206 (M2) macrophages is a significant predictor of progression-free survival univariately and is also significant after adjusting for race and for HER2, respectively. We examined whether the high numbers of TAMs detected in tumors from black women were associated with macrophage proliferation, using the Ki-67 nuclear proliferation marker. Our results reveal that TAMs actively divide when in contact with tumor cells. There is a higher ratio of proliferating macrophages in tumors from black patients. These findings suggest that interventions based on targeting TAMs may not only benefit breast cancer patients in general but also serve as an approach to remedy racial disparity resulting in better prognosis patients from minority racial groups.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Macrófagos/imunologia , Afro-Americanos , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Neoplasias da Mama/imunologia , Proliferação de Células , Intervalo Livre de Doença , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Lectinas Tipo C/metabolismo , Macrófagos/patologia , Lectinas de Ligação a Manose/metabolismo , Prognóstico , Receptores de Superfície Celular/metabolismo , Análise de Sobrevida
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