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2.
J Cutan Med Surg ; 17(5): 356-61, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24067858

RESUMO

BACKGROUND: Kaposi sarcoma (KS) is a cutaneous endothelial vascular proliferation with four subtypes: iatrogenic, acquired immune deficiency syndrome (AIDS) related, African, and classic. Familial cases of KS are rare, with 72 cases reported to date, and all were described with the classic variant. The occurrence of classic KS in the Jewish population is well documented, and most of the familial classic KS cases were also reported in Jewish families. OBJECTIVE: We briefly present the history, biopsies, laboratory data, diagnosis, and treatment of localized lower limb classic KS in two siblings of Jewish Eastern European ethnic descent with their response to different therapy modalities. One of our cases had the second longest reported period of follow-up for familial classic KS of 40 years.


Assuntos
Judeus , Sarcoma de Kaposi/etnologia , Sarcoma de Kaposi/patologia , Irmãos/etnologia , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Extremidade Inferior , Masculino , Sarcoma de Kaposi/terapia , Neoplasias Cutâneas/terapia
3.
PLoS One ; 6(12): e28250, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22163003

RESUMO

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours.


Assuntos
Cromossomos Humanos Par 3 , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único , Aberrações Cromossômicas , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes ras , Estudo de Associação Genômica Ampla , Genômica , Genótipo , Homozigoto , Humanos , Mutação , Metástase Neoplásica , Neoplasias Ovarianas/patologia , Ovário/metabolismo
4.
Oral Oncol ; 47(6): 441-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21514211

RESUMO

The aim of the present study was to investigate the available literature regarding the oral side effects or adverse events associated with targeted cancer therapy. Common oral toxicities include the terms mucositis, stomatitis, dysphagia, xerostomia, pharyngitis, and taste alterations. Aims of treatment included molecules and pathways involved in carcinogenesis reported in the literature were EGFRI, VEGF, mTOR, mAbs, TKIs, and multi-kinase inhibitors. Common targeted therapies used in clinical practice or under-investigation included cetuximab, panitumumab, erlotinib, sorafenib, sunitinib malate, imatinib mesylate, bevacizumab, trastuzumab, lapatinib, and mTORs. One hundred and forty-three articles were considered relevant and included in this review. The majority of studies did not specifically address oral toxicities or include an oral clinical exam, which may lead to underreported and under-investigated oral toxicities. Further investigation is necessary to determine if the initial impression that targeted therapy produces milder oral toxicities than conventional cancer treatment is accurate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transtornos de Deglutição/induzido quimicamente , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Terapia de Alvo Molecular/efeitos adversos , Mucosite/induzido quimicamente , Faringite/induzido quimicamente , Xerostomia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transtornos de Deglutição/terapia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Mucosite/terapia , Faringite/terapia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Xerostomia/terapia
5.
J Chemother ; 20(1): 28-32, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18343740

RESUMO

Daptomycin is a cyclic lipopeptide with potent bactericidal activity against Gram-positive organisms and has been approved by the United States Food and Drug Administration for the treatment of Staphylococcus aureus bacteremia and infectious endocarditis (right-side). We evaluated the activity of daptomycin against bloodstream infection S. aureus strains from 4,799 patients hospitalized in 32 medical centers (12 European countries, Turkey and Israel) with bloodstream infections (BSI) during a 5-year period (2002-2006). Intravenous catheters were the source of infection in 15% of cases, and those strains were analyzed separately. All strains were susceptibility tested by reference broth microdilution methods utilizing calcium supplementation (50 mg/L) when testing daptomycin. Bactericidal activity of daptomycin and vancomycin were evaluated against a subset of 50 randomly selected strains. Daptomycin (MIC(50/90), 0.25/0.5 mg/L), vancomycin (MIC (50/90), 1/1 mg/L), and linezolid (MIC(50/90), 2/2 mg/L), were highly active (>99.9% susceptibility) against the strains evaluated; and daptomycin was the most potent (lowest MIC(90) ) among these compounds. Resistance rates to oxacillin and levofloxacin were generally elevated, especially when an intravenous catheter was the source of infection.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Daptomicina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Cateteres de Demora/efeitos adversos , Cateteres de Demora/microbiologia , Europa (Continente) , Hospitalização , Humanos , Testes de Sensibilidade Microbiana , Oriente Médio , Infecções Estafilocócicas/microbiologia
6.
Nephrol Ther ; 3(4): 152-6, 2007 Jul.
Artigo em Francês | MEDLINE | ID: mdl-17658442

RESUMO

To date, more than 200 cases of nephrogenic systemic fibrosis have been documented worldwide. All patients have had renal failure, most of them requiring dialysis. We herein describe the course of a hemodialyzed patient who developed nephrogenic systemic fibrosis in the months following magnetic resonance angiography of the lower extremities. The disease is characterized by skin thickening and tendon fibrosis leading to joint contractures that can quickly confine the patient to a wheelchair. Systemic involvement may occur, leading to cardiomyopathy, pulmonary fibrosis, pulmonary hypertension or even death. No consistently effective therapy has been reported. An association between gadolinium exposure and the development of the disease has been found, although no causal link has yet been proven. In a patient with renal failure, magnetic resonance imaging with gadolinium enhancement should be done only after having seriously considered the risk/benefit ratio. Implications concerning the choice of imaging methods when searching for ischemic nephropathy or aorto-iliac disease before renal transplantation are discussed.


Assuntos
Fibrose/etiologia , Insuficiência Renal/complicações , Biópsia , Fibrose/patologia , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/patologia , Pele/patologia
7.
J Cutan Med Surg ; 11(1): 35-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17274937

RESUMO

BACKGROUND: Perifolliculitis capitis abscedens et suffodiens (PCAS) is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. This condition often presents in males of African American origin. OBJECTIVE: This article describes the clinical presentation, diagnosis, and treatment of an Aboriginal Canadian male suffering from PCAS. A literature review on the etiology, pathology, differential diagnosis, and management is also discussed. CONCLUSION: Careful analysis of the pathology and clinical presentation can aid in the timely diagnosis and management of this challenging condition. The clinician dealing with patients suffering from PCAS has several treatment options available to help successfully manage patients with straightforward or recalcitrant disease.


Assuntos
Foliculite/diagnóstico , Dermatoses do Couro Cabeludo/diagnóstico , Adolescente , Fármacos Dermatológicos/uso terapêutico , Foliculite/tratamento farmacológico , Humanos , Isotretinoína/uso terapêutico , Masculino , Dermatoses do Couro Cabeludo/tratamento farmacológico , Supuração
10.
Clin Nephrol ; 65(1): 13-21, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16429837

RESUMO

Indinavir is a potent HIV-1 protease inhibitor included in current antiretroviral therapeutic regimens. It is associated with renal and urological complications ascribed to indinavir crystalluria. We have previously reported that indinavir crystalluria is frequently observed soon after initiation of therapy. In a cohort of 54 asymptomatic indinavir-naive HIV-1-infected individuals during their first year of treatment with indinavir, approximately 25% of urinalyses (U/A) contained indinavir crystals. Because the determinants of the crystalluria are unknown, we examined the relationship between urine specific gravity (SG) and pH, singly and in combination, and indinavir crystalluria in these subjects. A total of 579 U/A were obtained from the study subjects at their scheduled monthly outpatient medical assessments. The frequency of indinavir crystalluria was lower in U/A with lower pH, irrespective of the SG. Conversely, U/A with high pH (> or = 6.0) had a higher frequency of indinavir crystalluria, which was further influenced by the urine SG. As a result, nearly half of the U/A (46.7%) with high pH (> or = 6.0) and intermediate-high SG (> or = 1.015) contained indinavir crystals. In conclusion, the frequency of indinavir crystalluria in asymptomatic HIV-1 infected individuals during their first year of treatment with indinavir was markedly influenced by the urine pH and SG. Our findings suggest that low urine pH may have a protective effect against indinavir crystalluria across the entire range of urine SG.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/urina , Infecções por HIV/tratamento farmacológico , Infecções por HIV/urina , Indinavir/uso terapêutico , Indinavir/urina , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Cristalização , Feminino , Humanos , Concentração de Íons de Hidrogênio , Indinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Gravidade Específica , Urinálise , Urina
11.
J Clin Pathol ; 58(10): 1086-90, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16189156

RESUMO

BACKGROUND: Her2 (c-erbB-2/neu) overexpression in breast carcinoma predicts response to the anti-Her2 monoclonal antibody, trastuzumab, and is associated with a poor prognosis. When considering patients for trastuzumab treatment, Her2 protein expression is measured by imunohistochemistry (IHC) and, where staining is equivocal, by fluorescence in situ hybridisation (FISH) detection of Her2 gene amplification. AIMS: To compare IHC using CBE356 with IHC using the Food and Drug Administration approved HercepTesttrade mark. METHODS: CBE356 and HercepTest were analysed using 167 FISH characterised breast carcinomas. Immunohistochemical expression of Her2 was measured semiquantitatively. Sensitivity, specificity, predictive values, and overall accuracy were calculated for both IHC methods using gene amplification by FISH as the end point, and IHC and FISH assays were tested in Kaplan-Meier survival analysis. RESULTS: The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CBE356 positive (2+ and 3+) cases were 94%, 89%, 95%, 84%, and 97%, respectively, and of HercepTest positive (2+ and 3+) cases were 91%, 66%, 98%, 92%, and 91%, respectively. A positive result with CBE356, HercepTest, or FISH was associated with significantly decreased overall survival (log rank p = 0.005, p = 0.0017, and p = 0.0005, respectively). CONCLUSIONS: Positive IHC staining for Her2 using CBE356 is 3% more accurate and 23% more sensitive at predicting Her2 gene amplification by FISH than positive staining with HercepTest. Negative IHC using CBE356 antibody is 6% more likely to represent a truly negative result than negative staining with HercepTest. Overall, CBE356 was a more accurate predictor of Her2 gene amplification by FISH than HercepTest.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/imunologia , Neoplasias da Mama/genética , Feminino , Seguimentos , Amplificação de Genes , Genes erbB-2 , Humanos , Hibridização in Situ Fluorescente/métodos , Pessoa de Meia-Idade , Prognóstico , Kit de Reagentes para Diagnóstico , Receptor ErbB-2/imunologia , Sensibilidade e Especificidade , Análise de Sobrevida
12.
Injury ; 36(10): 1190-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16185691

RESUMO

This study reports the early results for clinical and radiological outcome of fixation of completely displaced or grossly angulated (>90 degrees ) 2 and 3 part fractures of the proximal humerus using the PlantTan Fixator Plate (Medizentechnik, Aachen, Germany). Using a deltopectoral approach the humeral head articular fragment was reduced onto the humeral shaft and fixed with the implant, tuberosity fragments were held with transosseous sutures. Early passive, progressing to active, physiotherapy was instituted from the first postoperative day. No other fixation or bone graft was used. In 15 patients, with 16 injured shoulders and an average age of 63 years the mean follow up was 17 months. As a percentage of the normal side the Constant-Murley score for those patients retaining the implant was mean 74% (range 36%-100%). There were six shoulders with score >80% (Good), four shoulders with score between 60 and 79% (Satisfactory) and four shoulders <60% (Poor). Four shoulders (all in patients over the age of 70 years), developed avascular necrosis. Of these, one patient underwent shoulder replacement hemiarthroplasty and one patient underwent removal of the implant. We have demonstrated functional outcome similar to other modes of internal fixation in patients under 70 years. It cannot be recommended for elderly patients (over 70 years) as it is associated with a high incidence of avascular necrosis and fixation failure.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/instrumentação , Fraturas do Ombro/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose/etiologia , Radiografia , Reoperação , Fraturas do Ombro/diagnóstico por imagem , Resultado do Tratamento
13.
J Am Acad Dermatol ; 52(2 Suppl 1): 31-4, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15692509

RESUMO

BACKGROUND: Classic Kaposi's sarcoma (KS) is predominantly a disease of eastern Mediterranean and Ashkenazi Jewish elderly men. Nevertheless, the disease has been reported to occur in people from various other ethnic and regional backgrounds. OBJECTIVE: We report, for the first time, the occurrence of classic KS in five Inuit people living in northern Quebec, Canada. METHODS AND RESULTS: We describe the case of a 69-year-old Inuit man with classic KS, and report four other cases of KS in the Inuit population, identified by a review of our hospital's dermatopathology records. CONCLUSION: The discovery of classic KS in the Inuit population of northern Quebec brings with it new questions as to the origins of the KS-associated herpes virus in this population. It is our belief that the answers to these questions are in the genotype of the virus that is present in this community.


Assuntos
Inuíte , Sarcoma de Kaposi/etnologia , Neoplasias Cutâneas/etnologia , Idoso , Feminino , Doenças do Pé/etnologia , Doenças do Pé/patologia , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Quebeque , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/patologia
14.
Br J Cancer ; 90(2): 483-91, 2004 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-14735197

RESUMO

There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone.


Assuntos
Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA , Genes BRCA2 , Mutação em Linhagem Germinativa , Proteínas/genética , Proteínas Proto-Oncogênicas , Adulto , Idoso , Sequência de Bases , Análise Mutacional de DNA , Reparo do DNA , DNA Complementar , Feminino , Ligação Genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteína 2 Homóloga a MutS , Neoplasias Primárias Múltiplas , Linhagem , Reação em Cadeia da Polimerase
15.
Eur J Cancer ; 40(1): 56-63, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14687790

RESUMO

HER2/neu is an oncogene encoding a type 1 tyrosine kinase growth factor receptor. Polysomy 17, gene amplification and HER2/neu protein overexpression are associated with a poor prognosis in transitional cell carcinomas (TCC) of the bladder. Due to the application of different laboratory techniques, the exact incidence of HER/neu abnormalities remains uncertain in TCC. Standardised laboratory techniques are therefore important in the determination of the HER2/neu status if an assessment of the potential value of anti-HER2/neu treatments in the clinical management of patients with TCC is to be made. In this study, 75 TCCs with evidence of detrusor muscle invasion at first clinical presentation were included. Gene amplification, polysomy 17 and HER2 copy number were assessed using fluorescence in situ hybridisation (FISH), with separate probes for chromosome 17 and HER2/neu. Protein overexpression was assessed using immunohistochemistry (IHC), with the CB11 antibody and a scoring system evaluating only membranous staining as positive. The mean patient age was 69.5 years (range 42-93 years) and the median survival was 15 months (range 1-156 months). Polysomy 17 occurred in 97%, increased HER/neu copy number in 92% and HER2/neu gene amplification in 7%. Protein overexpression occurred in 57% of cases. Polysomy 17 and HER2/neu protein overexpression are common in G3 pT2 TCCs of the bladder. However, gene amplification is uncommon. Mechanisms other than gene amplification may be responsible for protein overexpression in this tumour type. Evidence from breast cancer suggests that only tumours with HER2/neu gene amplification respond to the anti-HER2/neu therapy trastuzumab (Herceptin). If this were true for bladder cancer, only 4/75 (5%) of G3 pT2 TCCs would be suitable for treatment. The role of trastuzumab in these tumours remains untested at present.


Assuntos
Carcinoma de Células de Transição/genética , Genes erbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/metabolismo , Cromossomos Humanos Par 17/genética , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo
16.
Br J Cancer ; 89(7): 1305-9, 2003 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-14520464

RESUMO

The mortality from transitional cell carcinoma (TCC) of the urinary bladder increases significantly with the progression of superficial or locally invasive disease (pTa/pT1) to detrusor muscle-invasive disease (pT2+). The most common prognostic markers in clinical use are tumour stage and grade, which are subject to considerable intra- and interobserver variation. Polysomy 17 and HER2/neu gene amplification and protein overexpression have been associated with more advanced disease. Standardised techniques of fluorescence in situ hybridisation and immunohistochemistry, which are currently applied to other cancers with a view to offering anti-HER2/neu therapies, were applied to tumour pairs comprising pre- and postinvasive disease from 25 patients undergoing treatment for bladder cancer. In the preinvasive tumours, increased HER2/neu copy number was observed in 76% of cases and increased chromosome 17 copy number in 88% of cases, and in the postinvasive group these values were 92 and 96%, respectively (not significantly different P=0.09 and 0.07, respectively). HER2 gene amplification rates were 8% in both groups. Protein overexpression rates were 76 and 52%, respectively, in the pre- and postinvasive groups (P=0.06). These results suggest that HER2/neu abnormalities occur prior to and persist with the onset of muscle-invasive disease. Gene amplification is uncommon and other molecular mechanisms must account for the high rates of protein overexpression. Anti-HER2/neu therapy might be of use in the treatment of TCC.


Assuntos
Carcinoma de Células de Transição/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/patologia , Cromossomos Humanos Par 17/genética , Progressão da Doença , Feminino , Amplificação de Genes , Dosagem de Genes , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Receptor ErbB-2/genética , Neoplasias da Bexiga Urinária/patologia
17.
Can J Urol ; 10(4): 1947-9, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14503941

RESUMO

A 75 year-old uncircumcised man presented with a 1.1mm thick malignant melanoma on the ventral aspect of the glans penis. He underwent isosulfan blue and technetium 99m guided sentinel lymph node (SLN) biopsy and distal penectomy with 2 cm margins. This is the third reported case of penile melanoma using both markers for SLN mapping. While frozen sections and H& E stains were negative, S-100 and HMB-45 immunohistochemistry revealed micrometastasis in one of the sentinel nodes. This case illustrates that any discussion with the patient about management and prognosis should await immunohistochemistry results.


Assuntos
Secções Congeladas/métodos , Melanoma/patologia , Melanoma/secundário , Neoplasias Penianas/patologia , Corantes de Rosanilina , Biópsia de Linfonodo Sentinela/métodos , Idoso , Biópsia , Humanos , Canal Inguinal/cirurgia , Metástase Linfática , Masculino , Melanoma/química , Melanoma/cirurgia , Neoplasias Penianas/química , Neoplasias Penianas/cirurgia , Corantes de Rosanilina/análise , Sensibilidade e Especificidade
18.
J Pathol ; 199(4): 418-23, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12635131

RESUMO

Accurate diagnostic assessment of HER-2 is essential for the appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with metastatic breast cancer. The diagnostic test needs to be applicable to archival, fixed tissue removed at excision, in many cases several years earlier. We compared the assessment of HER-2 by immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridization (FISH) in 426 breast carcinomas from patients being considered for trastuzumab therapy. The tumours were tested in three reference centres having been sent in from 37 hospitals. Only 2/270 (0.7%) IHC 0/1+ tumours were FISH positive. Six of 102 (5.9%) IHC 3+ tumours were FISH negative. Five of the six had between 1.75 and 2.0 HER-2 gene copies per chromosome 17 and the sixth had multiple copies of chromosome 17. Thirteen per cent of tumours were IHC 2+ and overall 48% of these were FISH positive but this proportion varied markedly between the centres. Sixty IHC-stained slides selected to be enriched with 2+ cases were circulated between the three laboratories and scored. There were 20 cases in which there was some discordance in scoring. Consideration of the FISH score in these cases led to concordance in the designation of positivity/negativity in 19 of these 20 cases. These data support an algorithm in which FISH testing is restricted to IHC 2+ tumours in reference centres. The results may not extrapolate to laboratories with less experience or using different methodologies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Algoritmos , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Metástase Neoplásica , Proteínas de Neoplasias/análise , Seleção de Pacientes , Receptor ErbB-2/imunologia , Reprodutibilidade dos Testes , Trastuzumab
19.
Breast Cancer Res Treat ; 77(2): 109-14, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12602909

RESUMO

Aberrations of chromosome 17 are common in breast cancer. Fluorescence in situ hybridization (FISH) enables gene or chromosome copy number to be assessed in situ in archival tissues and related to morphology and clinical outcome. In this study direct labeled DNA probes for the chromosome 17 alpha satellite and the HER2/neu gene were applied simultaneously to 5 micron sections of 214 formalin-fixed paraffin-embedded invasive primary breast carcinomas. A high proportion (54%) of invasive breast carcinomas displayed aneusomy of chromosome 17. Polysomy 17 correlated with multiple copies of HER2/neu (p = < 0.001), but not with HER2/neu amplification. Eighty-six patients without HER2/neu amplification had aneusomy 17. Fifty-eight of the 86 patients that had aneusomy 17 had high HER2/neu copy number. Twelve patients with normal copy number for chromosome 17 had amplification of HER2/neu and 30 patients had amplification of HER2/neu with aneusomy 17. Aneusomy 17 was associated with grade 3 carcinoma (p = 0.008), ER negativity (p = 0.0032) and a Nottingham prognostic index of greater than 5.4 (p = 0.039) but was not associated with survival by univariate analysis. In conclusion, the determination of chromosome 17 copy number should be incorporated in assessment of HER2/neu status, as this will give an accurate measure of amplification of HER2/neu and may also be helpful in determining suitability for breast carcinoma trials.


Assuntos
Aneuploidia , Neoplasias da Mama/genética , Cromossomos Humanos Par 17/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Sondas de DNA/genética , Feminino , Dosagem de Genes , Genes erbB-2/genética , Humanos , Hibridização in Situ Fluorescente/métodos , Pessoa de Meia-Idade , Prognóstico
20.
Scand J Rheumatol ; 31(6): 371-3, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12492254

RESUMO

We describe a patient with Grave's discase who developed purpura fulminans and who was found to have anticardiolipin antibodies after being started on propylthiouracil (PTU). We discuss the potential role of the antiphospholipid antibody in this woman's presentation, and its association to both PTU and autoimmune thyroid disease.


Assuntos
Anticorpos Anticardiolipina/imunologia , Antitireóideos/efeitos adversos , Doença de Graves/tratamento farmacológico , Vasculite por IgA/induzido quimicamente , Propiltiouracila/efeitos adversos , Adulto , Anticorpos Anticardiolipina/análise , Antitireóideos/uso terapêutico , Feminino , Doença de Graves/imunologia , Doença de Graves/patologia , Humanos , Vasculite por IgA/patologia , Propiltiouracila/uso terapêutico
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