RESUMO
OBJECTIVE: This review aimed to critically analyse data pertaining to the clinical presentation and treatment of neuroendocrine carcinomas of the larynx. METHOD: A PubMed search was performed using the term 'neuroendocrine carcinoma'. English-language articles on neuroendocrine carcinoma of the larynx were reviewed in detail.Results and conclusionWhile many historical classifications have been proposed, in contemporary practice these tumours are sub-classified into four subtypes: carcinoid, atypical carcinoid, small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. These tumours exhibit a wide range of biological behaviour, ranging from the extremely aggressive nature of small and large cell neuroendocrine carcinomas, which usually have a fatal prognosis, to the less aggressive course of carcinoid tumours. In small and large cell neuroendocrine carcinomas, a combination of irradiation and chemotherapy is indicated, while carcinoid and atypical carcinoid tumour management entails conservation surgery.
Assuntos
Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/terapia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/terapia , Fenótipo , Protocolos Antineoplásicos , Tumor Carcinoide/genética , Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/terapia , Tratamento Conservador/métodos , Humanos , Neoplasias Laríngeas/patologia , Laringe/patologia , Laringe/cirurgia , PrognósticoRESUMO
Laryngeal biopsies, contrary to biopsies from many other sites of the body, very often contain minute amounts of tumour tissue that may consist of morphologically undifferentiated tumour only. In haematoxylin- and eosin-stained sections, there may be no indicative features of what specific tumour entity that is present. In the larynx, particularly small round cell neoplasms, primary or metastatic, often cause a diagnostic dilemma and where an incorrect diagnosis can induce substantial clinical consequences for the patient (e.g., primary neuroendocrine carcinomas vs metastatic variants, certain sarcomas). If sufficient/representative material has been obtained, the application of immunohistochemistry and/or molecular techniques should in virtually every case reveal the true nature of the malignancy. In cases with sparse amount of material, and therefore a limited number of sections to be cut, a careful and thoughtful stepwise approach is necessary to ascertain a reliable diagnosis, or at least guide the clinician to the most likely diagnoses. With today's advanced and widely available technology with an abundance of markers to discriminate different tumours, the use of the term "undifferentiated" should be largely unnecessary. In the exceptional, and indeed exceedingly rare cases, when a classification is not possible, even after repeat biopsy, we suggest that the laryngeal neoplasm is better termed "unclassified malignant neoplasm" rather than "undifferentiated malignant neoplasm".
Assuntos
Neoplasias Laríngeas/classificação , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/patologia , HumanosRESUMO
Rare complication of radical surgery (Caldwell Luc procedure) of the maxillary sinus, maxillary cyst can occurred several years after. We describe the case of a patient 56 years old, who came to our consultationfor repeated pain in the right maxillary region with moderate facial asymmetry. In her history we noted a previous sinus surgery (Caldwell Luc) more than 10 years before. The imaging showed an expansive process filled with proteinic tissue of the posterior wall of the maxillary. With the history of the former surgery, we suspected the existence of a mucocele. She underwent an endonasal surgery and the pathological examination of the specimen revealed an intra osseous cyst lined with ciliated respiratory type mucosa post surgery of the maxillary sinus. The diagnosis of a maxillary cyst complicating a Caldwell Luc was established based on the results obtained with the clinico-radiological and pathological results.
Assuntos
Cistos/etiologia , Seio Maxilar/cirurgia , Doenças dos Seios Paranasais/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Nasais/efeitos adversosRESUMO
Verrucous carcinoma (VC) is a variant of squamous cell carcinoma (SCC), characterised by its inability to metastasize. In contrast, hybrid carcinomas, composed of VC and foci of conventional SCC, harbour a metastatic potential. Correct pathohistological diagnosis is therefore crucial for the choice of treatment. There is mounting evidence that desmosomes are involved in several aspects of carcinogenesis. Previous studies have shown an altered expression of desmosomal components in conventional SCC, which was associated with tumour behaviour, but no data have been found on desmosomes in VC. We therefore analysed the expression of desmosomal components in biopsy samples of 21 cases of VC and 5 cases of hybrid carcinoma of the head and neck in comparison to 23 cases of conventional SCC and 47 samples of normal squamous epithelium of similar localisation, using immunohistochemistry and real-time reverse-transcription polymerase chain reaction. We found that the expression patterns of desmosomal components in VC were fairly similar to those in normal epithelium but differed significantly from those in conventional SCC. Immunohistochemical reactions against desmosomal components disclosed the foci of SCC in hybrid carcinomas. In conclusion, we believe that expression patterns of desmosomal components in VC are consistent with its less aggressive behaviour. Differential expression of desmosomal components between VC and SCC makes some desmosomal components potentially useful in the diagnostics of VC, especially for the detection of hybrid carcinoma.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma Verrucoso/diagnóstico , Desmossomos/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma Verrucoso/genética , Carcinoma Verrucoso/metabolismo , DNA de Neoplasias/análise , Desmocolinas/genética , Desmocolinas/metabolismo , Desmogleínas/genética , Desmogleínas/metabolismo , Desmossomos/genética , Desmossomos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/metabolismo , Placofilinas/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adulto JovemRESUMO
BACKGROUND: Mucoepidermoid carcinoma (MEC) shows differences in biological behaviour depending mainly on its histological grade. High-grade tumours usually have an aggressive biological course and they require additional oncological treatment after surgery. METHODS: In a series of 43 MECs of the salivary glands, we studied the epidermal growth factor receptor (EGFR) gene by using dual-colour chromogenic in situ hybridisation (CISH). Moreover, we assessed the protein expressions of the EGFR and the activated extracellular signal-regulated kinases (pERK1/2) by using immunohistochemistry. These results were correlated with the histological grade of the tumours and the outcome of the patients. RESULTS: The CISH study demonstrated a high-EGFR gene copy number, with balanced chromosome 7 polysomy, in 8 out of 11 high-grade MECs (72.7%), whereas 27 low-grade and 15 intermediate-grade tumours had a normal EGFR gene copy number (P<0.001). The EGFR gene gains correlated with disease-free interval (P=0.003) and overall survival of the patients (P=0.019). The EGFR protein expression had a significant correlation with the histological grade of the tumours but not with the outcome of the patients. The pERK1/2 expression correlated with histological grade of tumours (P<0.001), disease-free interval (P=0.004) and overall survival (P=0.001). CONCLUSIONS: The EGFR/ERK pathway is activated in high-grade MECs with aggressive behaviour. Patients with these tumours who require oncological treatment in addition to surgery could benefit from EGFR and mitogen-activated protein kinase pathway inhibitors.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/terapia , Criança , Pré-Escolar , Receptores ErbB/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapia , Transdução de Sinais , Adulto JovemRESUMO
OBJECTIVES: Neoplasms associated with human papillomavirus (HPV) infection occur at increased frequency in patients with HIV infection/AIDS. Although laryngeal squamous cell carcinomas (LSCCs) in HIV-positive patients are uncommon, a higher incidence of this malignancy in HIV-positive patients than in the general population has been reported. As a proportion of LSCCs are associated with HPV in the general population, the clinicopathological features of a series of LSCCs developing in HIV-positive patients were evaluated to investigate the possible relationship with HPV infection, and infection with other oncogenic viruses. METHODS: All HIV-positive patients with LSCC diagnosed at a single institution from 1998 to 2007 were retrospectively evaluated. The clinicopathological features were analysed and tissues were tested by polymerase chain reaction (PCR), using the short PCR fragment 10 (SPF10) primer, a highly sensitive method for HPV DNA detection. Immunohistochemical studies for HIV p24, p16(INK4a) and p53 were performed. Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8) were also investigated. RESULTS: Six out of 4987 HIV-infected patients seen in this period in the Infectious Diseases Department developed LSCC (median age 41.5 years; male to female ratio 1:1). All patients were heavy smokers and the tumours presented at an advanced clinical stage. HPV was not detected in any tumour, not even in two patients with coexisting HPV-associated gynaecological neoplasm. Staining for HIV p24 and p16(INK4a) was negative, whereas p53 was positive in half the cases. EBV and HHV-8 were also negative. CONCLUSION: LSCC developing in HIV-positive patients is an infrequent neoplasm, not usually associated with HPV infection. It develops in young, heavy smokers and presents at an advanced clinical stage.
Assuntos
Carcinoma de Células Escamosas/virologia , Infecções por HIV/complicações , Neoplasias Laríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Adulto , Fatores Etários , Carcinoma de Células Escamosas/epidemiologia , DNA Viral/análise , Feminino , Infecções por HIV/epidemiologia , HIV-1 , Humanos , Neoplasias Laríngeas/epidemiologia , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Reação em Cadeia da Polimerase/métodos , RNA Viral/análise , Estudos Retrospectivos , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
We describe a rare case of metastasis to the pa ra - na sal sinuses. The lesion had an immunohistochemical (positivity for cytokeratin 20, negativity for cytokeratin 7, overexpression of p53) and in situ hybridisation profile (neither lesions showed deletion for p53) consistent with metastasis from the earlier rectal adenocarcinoma. The correct typification of intestinal-type neoplasms requires a combination of morphological, immunohistochemical and, sometimes, molecular analysis.
Assuntos
Adenocarcinoma/secundário , Cavidade Nasal/patologia , Neoplasias dos Seios Paranasais/secundário , Neoplasias Retais/patologia , Adenocarcinoma/patologia , Idoso , Feminino , Humanos , Imuno-Histoquímica , Invasividade Neoplásica/patologia , Neoplasias dos Seios Paranasais/patologiaRESUMO
UNLABELLED: The product of the ATM gene, mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a key role in the detection and repair of DNA double-strand breaks. A-T is defined by progressive cerebellar ataxia, telangiectasia, sensitivity to ionising radiation and genomic instability with cancer predisposition. On the other hand, increased angiogenesis is essential for tumor growth and metastasis. The aim of this study was to investigate ATM expression in breast carcinomas and its relationship to neoangiogenesis. METHODS AND RESULTS: Fifty-two breast tumors from 51 patients, 38 of them with concomitant in situ component (CIS), were analyzed by immunohistochemistry for the expression of ATM. CD34 expression was used for the morphometric evaluation of vasculature. ATM was positive in 1 to 10% of normal epithelial cells. ATM expression was reduced in 55.8% of infiltrating carcinomas, non-reduced in 34.6%, and increased in 9.6%. Expression of ATM in CIS was similar to the infiltrating component in 71% of cases and reduced in 23.7% of them. High-grade ductal infiltrating carcinomas showed lower ATM expression than low-grade ones. Reduced ATM expression also correlated with increased microvascular area. CONCLUSIONS: Reduced ATM expression in breast carcinomas correlated with tumor differentiation and increased microvascular parameters, supporting its role in neoangiogenesis and tumor progression in breast carcinogenesis.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Neovascularização Patológica/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Antígenos CD34/análise , Proteínas Mutadas de Ataxia Telangiectasia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/irrigação sanguínea , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Proteínas de Ciclo Celular/fisiologia , Diferenciação Celular , Dano ao DNA , Proteínas de Ligação a DNA/fisiologia , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Neovascularização Patológica/fisiopatologia , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Supressoras de Tumor/fisiologiaRESUMO
OBJECTIVE: We analyzed the value of topoisomerase IIalpha (Topo II) in predicting the clinical response to anthracycline-based neoadjuvant chemotherapy in breast cancers and the potential changes in Topo II after chemotherapy. In parallel, HER2, which is commonly coexpressed with Topo II, and p53, a modulator of chemotherapy activity, were also analyzed. METHODS: Forty-one patients with primary breast cancer and treated with neoadjuvant anthracycline-based chemotherapy (FAC or FEC) were included for the present study. Topo II, HER2 and p53 expression were measured by immunohistochemistry in pre and post chemotherapy (at the time of surgery), tumor specimens and the results were correlated with the clinical response. RESULTS: Topo II was overexpressed in 16 of 41 (31%) tumors before treatment, and this overexpression was significantly associated with clinical response (p = 0.03). HER2 and p53 were unrelated to response. Notably, Topo II overexpression, but not HER2 or p53, was lost in specimens after chemotherapy (p = 0.01). CONCLUSION: The observed link between Topo II and the clinical response to neoadjuvant anthracycline-based chemotherapy, together with its loss after chemotherapy, implies that Topo II deserves further testing in a prospective setting as a predictive marker.
Assuntos
Antraciclinas/administração & dosagem , Neoplasias da Mama/enzimologia , DNA Topoisomerases Tipo II/metabolismo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Imuno-Histoquímica , Receptor ErbB-2/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
AIMS: Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely. METHODS AND RESULTS: All the patients were male with a peak incidence in the sixth decade of life. The tumours were located most frequently in the larynx and oral cavity, followed by the nasal cavity and pharynx. ASCs had two distinct histological components. The most extensive one was an usual keratinizing squamous cell carcinoma, arising from the surface epithelium, where characteristically severe dysplasia or carcinoma in situ was found in all cases. The second component was an adenocarcinoma, usually displayed in the deepest areas of the tumour. Evidence of origin from salivary or seromucinous glands was not found. Immunohistochemical studies demonstrated in most cases positivity of glandular differentiated areas for carcinoembryonic antigen (CEA) (11/12), CK7 (9/12) and CAM5.2 (7/12), whereas the squamous cell component was unreactive or reacted only focally for these markers. High-molecular-weight cytokeratin 34BE12 was positive in both components and CK20 was always negative. All cases showed high expression of Ki67 antigen. Most of them had overexpression of p53 (8/12) and DNA aneuploidy (10/12). Fifty percent of patients with ASC died of disease after a mean period of 23 months (range 12-35 months). CONCLUSIONS: ASC of the head and neck is an aggressive neoplasm that originates in the surface epithelium of the upper respiratory tract. Severe dysplasia or carcinoma in situ is usually found and its recognition helps to make the diagnosis. In addition to mucin stains, positive immunoreactivity for CEA, CK7 and CAM5.2 helps to identify the glandular component.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Adenoescamoso/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Adulto , Idoso , Aneuploidia , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/mortalidade , DNA de Neoplasias/genética , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Análise de SobrevidaRESUMO
Ameloblastomas are the most frequent odontogenic tumours, accounting for 1% of all tumours of the maxilla and mandible. Sinonasal ameloblastomas are most common between the ages of 55 and 65, and mandibular ameloblastomas between 40 and 50. Incidence is higher in males than in females, and there are no differences between races. These locally aggressive tumours originate in the mandible in 80% of cases and in the maxilla in 15-20%. We report an unusual primary nasosinusal ameloblastoma presented in a 68-year-old male. The tumour was completely resected by (para)lateral rhinotomy and treated with postoperative radiotherapy. Histological analysis demonstrated a plexiform ameloblastoma. The patient remains well without disease after 50 months of postoperative follow-up.
Assuntos
Ameloblastoma/patologia , Invasividade Neoplásica/patologia , Neoplasias dos Seios Paranasais/patologia , Idoso , Ameloblastoma/radioterapia , Ameloblastoma/cirurgia , Biópsia por Agulha , Seguimentos , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Obstrução Nasal/diagnóstico , Obstrução Nasal/etiologia , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/radioterapia , Neoplasias dos Seios Paranasais/cirurgia , Radioterapia Adjuvante , Medição de Risco , Resultado do TratamentoRESUMO
We present the clinicopathological, histological and immunohistochemical findings of six cases of primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract with ultrastructural examination in one case. Due to its unique features, we believe that primary tubulopapillary low-grade adenocarcinoma of the sinonasal tract represents a tumour entity different from any tumours generally recognised in the sinonasal region. Our cases had an equal sex incidence, with an age range of 44-76 years. The tumour has a tendency to recur, but none of our six patients developed metastases. We feel that it is important to separate this tumour entity from other types of sinonasal adenocarcinomas that exhibit a papillary growth pattern, as they frequently pursue a much more aggressive clinical course than the tumours in this study.
Assuntos
Adenocarcinoma Papilar/patologia , Adenocarcinoma/patologia , Neoplasias dos Seios Paranasais/patologia , Adenocarcinoma/química , Adenocarcinoma/cirurgia , Adenocarcinoma Papilar/química , Adenocarcinoma Papilar/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/análise , Núcleo Celular/ultraestrutura , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Microscopia Eletrônica , Microvilosidades/ultraestrutura , Pessoa de Meia-Idade , Organelas/ultraestrutura , Neoplasias dos Seios Paranasais/química , Neoplasias dos Seios Paranasais/cirurgia , Resultado do TratamentoRESUMO
Fungal sinusitis is a rare entity which has increased amongst immunocompromised individuals. Records of thirteen patients treated of fungal sinus disease between 1995 and 2001 were reviewed. Histopathological studies demonstrated infection due to Aspergillus in eight patients and due to Mucormycosis in five patients. The surgical debridement via endoscopic sinus surgery was the essential part of the management. The follow-up is 12-72 months (mean 29.08). The main clinical findings and a review of the literature are presented. We conclude that endoscopic sinus surgery is the treatment of choice for fungal sinusitis except in advanced cases of mucormycosis in which a combined approach is still necessary together with intravenous antifungal drugs (amphotericin B).
Assuntos
Aspergilose/cirurgia , Desbridamento/métodos , Endoscopia , Mucormicose/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos , Sinusite/cirurgia , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Mucormicose/microbiologia , Estudos Retrospectivos , Rhizopus , Sinusite/tratamento farmacológico , Sinusite/epidemiologia , Sinusite/microbiologia , Espanha/epidemiologia , Resultado do TratamentoRESUMO
Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.
Assuntos
Adenocarcinoma/patologia , Mesonefroma/patologia , Mesonefro/patologia , Neprilisina/metabolismo , Neoplasias Uterinas/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Adulto , Antígenos de Neoplasias/metabolismo , Antígenos de Superfície/metabolismo , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Queratina-7 , Queratinas/metabolismo , Antígenos CD15/metabolismo , Mesonefroma/metabolismo , Mesonefroma/terapia , Mucina-1/metabolismo , Radioterapia Adjuvante , Resultado do Tratamento , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/terapia , Vimentina/metabolismoRESUMO
In immunoglobulin A nephropathy (IgAN), the abnormal expression of intercellular adhesion molecule-1 (ICAM-1) on proximal tubule epithelium is associated with the glomerular and interstitial infiltration of leucocytes, but its clinical significance remains uncertain. We analysed the relationship between the ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes, macrophages (CD14) and T lymphocytes (CD3) with the histologic features, proteinuria and serum creatinine at the time of renal biopsy and after 2.42 years in 45 patients with IgAN and after 1.8+/-1.5 years in 29 patients with non-glomerulonephritis (non-GN). In IgAN, ICAM-1+ tubule epithelium was 0.1+/-0.18 (x+/-SD), and this was associated with extracapillary proliferation (up to 20% of Bowman's space), glomerular sclerosis involving less than 50% of glomerular area, interstitial cellular infiltration, tubular atrophy and proteinuria level. ICAM-1+ interstitial leucocytes were correlated with glomerular sclerosis involving less than 50% of glomerular area, glomerular sclerosis involving more than 50% of glomerular area, tubular atrophy, interstitial fibrosis and serum creatinine level. In patients with an increase of 50% in serum creatinine, ICAM-1+, CD14+ and CD3+, interstitial leucocytes were significantly outnumbered than in patients with stable serum creatinine. In non-GN, ICAM-1+ tubule epithelium was 0.02+/-0.04 (U=344, P<0.05, vs IgAN), and this was inversely correlated with the percentage of the normal glomeruli and associated with glomerular sclerosis covering more than 50% of glomerular area, tubular atrophy and serum creatinine level. The association between tubular ICAM-1 and proteinuria and the association between interstitial ICAM-1+, CD14+ and CD3+, leucocytes and renal failure at presentation and the deterioration in IgAN in contrast with non-GN suggest that tubular and interstitial expression of ICAM-1 may be a marker of tubulointerstitial disturbance in IgAN.
Assuntos
Glomerulonefrite por IGA/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Túbulos Renais/metabolismo , Nefrite Intersticial/metabolismo , Adulto , Biomarcadores/análise , Feminino , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/patologia , Humanos , Técnicas Imunoenzimáticas , Rim/anatomia & histologia , Rim/metabolismo , Túbulos Renais/patologia , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/patologia , PrognósticoRESUMO
We describe a simple system of tissue arraying with multiple tissue fragments obtained with a biopsy punch from selected areas of paraffin blocks. The new blocks thus constructed allow multiple tissue sections in which the uniform shape of the fragments coupled with a geometrical display and a significant amount of tissue per case allows a dependable, cost-effective way to screen tumors or other kinds of tissues with techniques such as immunohistochemistry. This system avoids the disadvantages of previous laborious methods of tissue arraying, such as expensive equipment and scarce tissue sampling, and it can be implemented in any institution with minimal cost and elaboration.
Assuntos
Perfilação da Expressão Gênica , Técnicas Histológicas/métodos , Análise de Sequência com Séries de Oligonucleotídeos , DNA de Neoplasias/análise , Técnicas Histológicas/economia , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Patologia , RNA Mensageiro/biossíntese , RNA Neoplásico/análiseRESUMO
cdc25 is a family of cell-cycle phosphatases that activate the cyclin-dependent kinases. cdc25A and B, but not C, have oncogenic potential in vitro. In this study, we analyzed the possible implication of cdc25 genes in the progression of colorectal tumors. RNA and DNA were extracted from 34 paired tumor and normal colorectal tissues and examined by Northern blot, RT-PCR, and Southern blot, respectively. Protein expression was analyzed by Western blot in a subset of normal and tumor samples. The expression levels were correlated with the clinicopathologic characteristics and survival of the patients. cdc25B mRNA was overexpressed in 19 carcinomas (56%). A significant correlation was observed between high cdc25B mRNA levels and the relapse-free, overall, and cancer-related survival of the patients. The cdc25B2 splicing variant was detected in 27 carcinomas (79%) but only in 9 normal samples (26%) and was associated with the grade of the differentiation of the tumors. cdc25A mRNA was overexpressed in four tumors (12%) and cdc25C1 mRNA was overexpressed in nine tumors (26%). A new cdc25C2 splicing variant lacking exon 4 and 5 was identified in all of the tumors and in 56% of the normal samples. No amplifications or gene rearrangements of these genes were detected. In conclusion, these findings indicate that cdc25 isoforms and splicing variants are differentially regulated in colorectal carcinomas and may participate in the development of these tumors. Additionally, the correlation between cdc25B mRNA levels and the survival of the patients also suggest that the cdc25B isoform may be involved in the progression of the disease.
Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Fosfatases cdc25/genética , Adulto , Idoso , Processamento Alternativo , Southern Blotting , Carcinoma/metabolismo , Carcinoma/mortalidade , Colo/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Análise Mutacional de DNA , DNA de Neoplasias/análise , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Isoformas de Proteínas , RNA Mensageiro/biossíntese , Taxa de Sobrevida , Fosfatases cdc25/biossínteseRESUMO
Cathepsins B and S (CatB, CatS) are lysosomal cysteine proteases which, among other functions, appear to play a role in cancer progression in different tumor models due to their matrix-degrading properties. To investigate their possible involvement in the development of prostate carcinoma, we immunohistochemically analyzed CatB and CatS in 38 primary human prostatic adenocarcinomas, as well as concomitant high-grade prostatic intra-epithelial neoplasia, nodular hyperplasia and normal tissue. CatB expression was observed in 28 (74%) and CatS in 32 (84%) carcinomas, being concomitant in 24 cases (63%). High-grade intra-epithelial neoplasia expressed CatB in 20/23 cases (87%), and a similar result was obtained for CatS, with expression of both coinciding in 18 cases (78%). In non-neoplastic tissue, strong expression of both proteases was observed in macrophages, inflamed glands and transitional metaplasia, whereas atrophic glands and basal cells of normal glands displayed intense CatB positivity. We conclude that CatB and CatS are often expressed together in neoplastic prostatic cells from pre-invasive to invasive and clinically detectable stages, suggesting a putative role in local invasion, though other functions cannot be ruled out.
Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Catepsina B/biossíntese , Catepsinas/biossíntese , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Progressão da Doença , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologiaRESUMO
Immunosuppression, particularly of cell-mediated responses, has classically been thought to play a major role in the increased susceptibility to malaria observed in pregnant women. An immunohistochemical characterization of the inflammatory infiltrate in a group of 41 placentas from women living in a Plasmodium falciparum-hyperendemic area in Tanzania revealed a marked increase in the number of monocytes and macrophages and cytotoxic T cells in the intervillous space of placentas with active malaria infection, compared with noninfected placentas, placentas from women with past infection, and a control group of placentas from Spain. This increase was associated with the severity of the infection. High numbers of monocytes and macrophages were associated with low birth weight. We also detected a complete absence of NK cells in the intervillous space in all placentas. This apparently physiological absence of NK cells may contribute to hindering the clearance of the parasite. These results indicate that placental malaria does not appear to be associated with cell-mediated immunosuppression. The role of the absence of NK cells in increased susceptibility to malaria needs to be further elucidated.
Assuntos
Células Matadoras Naturais/imunologia , Malária Falciparum/imunologia , Placenta/imunologia , Plasmodium falciparum , Complicações Parasitárias na Gravidez/imunologia , Animais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígeno CD56/análise , Antígenos CD8/análise , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Inflamação/imunologia , Macrófagos/imunologia , Malária Falciparum/parasitologia , Monócitos/imunologia , Paridade , Placenta/parasitologia , Gravidez , Complicações Parasitárias na Gravidez/parasitologia , Linfócitos T Citotóxicos/imunologiaRESUMO
Alterations in expression of the p53 and cyclin D1 genes have been implicated in the development of esophageal carcinomas in both humans and animal models. We hypothesize that altered expression of cyclin D1 and p53 may be involved in the sequential development of esophageal carcinomas with glandular differentiation induced by the carcinogen, 2,6-dimethylnitrosomorpholine (DMNM) in rats with duodenal content reflux esophagitis. In the present study Sprague-Dawley rats were given DMNM 15 days after performing an esophago-jejunostomy in order to induce chronic duodenal content reflux esophagitis. Expression and localization of p53, cyclin D1 and Ki-67 were examined by immunohistochemical analyses. Twenty of 24 animals developed different types of esophageal carcinomas, including pure squamous carcinoma, adenosquamous carcinoma and pure adenocarcinoma. Undifferentiated basaloid areas were frequently observed in these tumors. Cyclin D1 overexpression was observed in hyperplastic lesions and increased through dysplasia and in undifferentiated areas of infiltrating carcinoma. Cyclin D1 expression coincided with increased Ki-67 expression and decreased along with cell differentiation. The p53 immunohistochemical pattern was parallel to that of cyclin D1, although the percentage of positive cells was usually smaller in all lesions and increased p53 expression started at the dysplastic stage. These findings suggest that overexpression of cyclin D1 may be an early event in DMNM-induced rat esophageal tumorigenesis, causing increased proliferation of esophageal stem cells. Abnormal p53 expression may then be required to promote the development of neoplastic transformation from dysplastic epithelium through invasive phenotype, being more evident in cancer cells with squamous differentiation.