RESUMEN
In medical care cervical cancer screening is important because it enables the detection of precancer and cancer at an early stage. By adequate treatment after a screening-detected lesion it helps to reduce the mortality related to cervical cancer. Worldwide, many millions of women have smears taken at a more or less regular base and of these, approximately 7% are abnormal, and follow-up is thus required.As this represents an important cost in medical health care and has serious consequences for the affected women, it is important to have uniform and clear guidelines to allow an optimal follow-up and clinical management. A system for the uniform reporting of cervical cytology has been designed by the National Cancer Institute (U.S.A.) and resulted in the Bethesda System 1991. The present paper and the terminology used are based on the Bethesda System revised in 2001. It explains the guidelines, based on the 2001 Bethesda System and the 2004 consensus guidelines for the management of women with cervical cytological abnormalities, as developed by the members of the Board of the Belgian Society of Clinical Cytology, and adapted to the Belgian situation.
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Tamizaje Masivo/métodos , Guías de Práctica Clínica como Asunto , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal/normas , Bélgica , Femenino , Estudios de Seguimiento , Humanos , Tamizaje Masivo/normasAsunto(s)
Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias Primarias Secundarias/patología , Derrame Pleural Maligno/etiología , Anciano , Humanos , Inmunohistoquímica , Leucemia Linfocítica Crónica de Células B/metabolismo , Linfoma de Células B/complicaciones , Linfoma de Células B/metabolismo , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/metabolismo , Masculino , Neoplasias Primarias Secundarias/complicaciones , Neoplasias Primarias Secundarias/metabolismo , Derrame Pleural Maligno/citología , Sarcoma de Kaposi/patologíaAsunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Frotis Vaginal , Factores de Edad , Bélgica/epidemiología , Femenino , Humanos , Tamizaje Masivo/estadística & datos numéricos , Tamizaje Masivo/tendencias , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Frotis Vaginal/estadística & datos numéricos , Frotis Vaginal/tendenciasRESUMEN
AIMS: The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy. METHODS AND RESULTS: The percentage of Ki67+ lesional nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters (defined as a group of at least two strongly Ki67+ nuclei located in the upper third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended on the proportion of the stained nuclei and on the intensity of staining. MiD, MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and 40% median values of positive cells). Thirty-one percent MiD, 77% MoD, 91% SD and 100% CIS showed one or more positive clusters. When only multiple clusters were considered the difference between high- and low-grade lesions was accentuated. Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD (15%) and MoD (22%). This difference was statistically significant (P < 0.01). Evaluation of the Ki67 score was in line with the above results: high grade lesions (SD and CIS) more often showed scores >4 (P = 0.05 between MiD plus MoD versus SD plus CIS). CONCLUSIONS: Ki67 expression increases from MiD to CIS with a statistically significant difference between MiD plus MoD and SD plus CIS. These results suggest that, in terms of Ki67 positivity, SD behaves like CIS rather than like MiD or MoD.
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Bronquios/metabolismo , Carcinoma in Situ/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Lesiones Precancerosas/metabolismo , Biopsia , Bronquios/patología , Broncoscopía , Carcinoma in Situ/clasificación , Carcinoma in Situ/patología , Recuento de Células , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/patología , Organización Mundial de la SaludRESUMEN
OBJECTIVE: Initially considered as an inhibitor of angiogenesis, the role of thrombospondin is currently controversial. The primary purpose of our study was to determine the expression of thrombospondin (TSP) in invasive lung tumours. The secondary objectives were to investigate its relationship with other factors related to angiogenesis and to assess their clinicopathological significance. MATERIALS AND METHODS: From January 1993 to September 1998, we collected non-small cell lung cancer (NSCLC) and normal nearby-matched tissues from surgical specimens of 64 patients. Using these specimens, we assessed the expression of TSP by immunohistochemistry with monoclonal antibody to human TSP (clone 11.4). This expression was also correlated with other factors directly or indirectly related to angiogenesis:p53, Ki-67 as proliferation factor and microvessel count determined with anti-CD-31 antibody. RESULTS: The resected tumours (stages I-IIIB) consisted of 30 adenocarcinomas, 24 squamous cell carcinomas, 5 bronchioalveolar carcinomas, 4 adenosquamous carcinomas and 1undifferentiated NSCLC. The mean values of TSP expression in neoplastic and normal related tissues were 63.08% and 86.57 %, respectively. This difference was statistically significant (p = 0.02). There was a higher level of variability of TSP expression between tumours than between normal tissues. The expression of TSP in NSCLC was statistically correlated to the expression of TSP in normal matched tissues (coefficient correLation rate = 0.31, p<0.01). The median expression of p53, Ki-67 and microvessel count in tumours was 45.00%, 38.80% and 8.33%, respectively. The correlations between TSP and the other biological variables and between these latter variables themselves were not statistically significant. No statistically significant difference was observed in survival according to TSP expression. CONCLUSION: TSP appeared to be decreased in NSCLC in comparison with normal matched tissue. The TSP expression was not correlated with the other studied variables and was not associated with a significant difference in survival.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Trombospondinas/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Antígeno Ki-67/biosíntesis , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/inmunología , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
BACKGROUND: The humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) is a new treatment modality for metastatic breast cancer, the efficacy of which is directly correlated with the HER-2 status of the tumour, evaluated either by immunohistochemistry (IHC) and/or by fluorescence in situ hybridisation (FISH). This analysis is generally performed on the primary tumour. There are few data regarding the HER-2 status in the corresponding distant metastases. METHODS: HER-2 status in 107 patients with a primary breast tumour and at least one distant metastatic lesion was analysed by IHC and FISH. RESULTS: We found similar levels of amplification (25% and 24%) and overexpression (13% and 19%) of HER-2 in primary and metastatic samples, respectively. Among paired primary/metastatic tumours, six (6%) showed discordance by HercepTest(TM) (n = 100): all six cases showed greater Her-2 overexpression in the metastatic tissue. By FISH (n = 68), five (7%) cases were discordant: two cases were amplified in the primary tumour but not in the metastasis, and three samples showed amplification in the metastasis but not in the primary. Finally, we analysed HER-2 status in different metastatic lesions from 17 patients that had at least two distant metastatic sites. Discordance between different sites from the same patient was 18% by IHC and 19% by FISH. CONCLUSIONS: Between the paired primary tumour and distant metastatic lesions, 94% and 93% of samples had concordant HER-2 status when analysed by IHC or FISH, respectively. These results do not support routine determination of HER-2 on metastatic sites, particularly when FISH results from the primary tumour are available.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Metástasis de la Neoplasia/patología , Neoplasias Primarias Múltiples/patología , Receptor ErbB-2/análisis , Biopsia con Aguja , Estudios de Cohortes , Intervalos de Confianza , Técnicas de Cultivo , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Estadificación de Neoplasias , Pronóstico , Muestreo , Sensibilidad y EspecificidadRESUMEN
Since tamoxifen therapy can induce endometrial disorders, surveillance schemes of women taking tamoxifen have been recommended. Transvaginal ultrasonography is a very sensitive test and therefore is often performed as a first-line screening test. We described a very atypical case of a high stage, high grade endometrial cancer associated with tamoxifen in a 64-year-old woman with a past history of breast cancer. This women was assessed yearly by ultrasonography and Pap smear. The cancer developed on a very thin endometrium and transvaginal ultrasonography failed to detect it. The patient remained asymptomatic up to the diagnosis. Normal endometrial cells in the Pap smear test were the only signs associated with this cancer. Surveillance strategies and significance of endometrial cells on the Pap smear are reviewed. In conclusion, TVUS can fail to detect cancers if the endometrial lining is not enlarged. In case of normal endometrial cells in the Pap smear, a careful evaluation should be performed.
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Carcinoma/inducido químicamente , Neoplasias Endometriales/inducido químicamente , Endosonografía/métodos , Tamoxifeno/efectos adversos , Vagina/diagnóstico por imagen , Biopsia con Aguja , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Carcinoma/terapia , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/cirugía , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Femenino , Humanos , Mastectomía Segmentaria/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Prueba de Papanicolaou , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Tamoxifeno/uso terapéutico , Vagina/patología , Frotis VaginalRESUMEN
AIMS: Tumour tissue microarray allows the analysis of hundreds of tumour samples simultaneously on a single microscope slide. However, the extremely small tissue samples taken from the original tissue may not always be representative of the entire tumour. METHODS: The reliability of this new technology was investigated by analysing HER-2 oncogene amplification by fluorescence in situ hybridisation (FISH) from representative slides of the whole tumour and small tissue core biopsies from 29 invasive breast tumours. RESULTS: The tissue microarray method had high accuracy; in only one of 29 cases (3.4%; 95% confidence interval, 0% to 10%) were the results discordant with whole tumour analysis. CONCLUSION: Tumour microarray is a highly reliable method for analysing HER-2 oncogene amplification by FISH in human breast tumours.
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Biomarcadores/análisis , Neoplasias de la Mama/genética , ADN de Neoplasias/genética , Genes erbB-2 , Análisis de Secuencia por Matrices de Oligonucleótidos , Biopsia con Aguja , Neoplasias de la Mama/patología , Reacciones Falso Negativas , Femenino , Humanos , Hibridación Fluorescente in Situ , Invasividad Neoplásica , Reproducibilidad de los ResultadosRESUMEN
p53 alteration has been reported to be an early event in bronchial carcinogenesis. Our study purpose was to determine the rate of p53 expression in the various preneoplastic and early neoplastic bronchial lesions obtained by biopsy during fluorescence bronchoscopy and to analyse its association with patients characteristics. Various stages of preneoplastic lesions as well as radio-occult lung cancer were studied in biopsies obtained by fluorescence bronchoscopy. We assessed the expression of p53 by immunohistochemistry using monoclonal antibody clone DO7. The p53 expression was considered as positive if > or = 1% of cells were positive and the level of positivity was expressed in percentage of positive cells. Fourteen patients were included in each category of preneoplastic lesions. At the threshold of 1% of positive cells p53 expression was observed in 28.5% of the patients with a histologically normal epithelium. This number of positive patients increased with the severity of preneoplastic lesions and reached 100% in the mild dysplasia. The mean rates of p53 positive cells for normal epithelium, hyperplasia, metaplasia, mild and severe dysplasia, carcinoma in situ and invasive radio-occult carcinoma were respectively 0.9, 3.4, 9.1, 20.5, 50.2, 34.7 and 42.5%. There was no statistically significant correlation between p53 expression and patient characteristics such as sex, age, smoking habits and indication for fluorescence bronchoscopy. The alteration of p53 expression in patients with high risk of lung cancer was an early event: this abnormality increased with the severity of the lesions, without significant correlation with patient characteristics.
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Neoplasias de los Bronquios/metabolismo , Carcinoma in Situ/metabolismo , Lesiones Precancerosas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Bronquios/patología , Carcinoma in Situ/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Metaplasia/metabolismo , Metaplasia/patología , Persona de Mediana Edad , Membrana Mucosa/metabolismo , Membrana Mucosa/patología , Estadificación de Neoplasias , Lesiones Precancerosas/patologíaRESUMEN
Present study consists of cytogenetic evaluation in 141 cases referred to our centre for various leukemias. This includes 110 cases of CML, 10 of ALL, 16 of AML (M3), 2 of AML(M2), 2 of MDS and 1 of CMML. The conventional cytogenetic study was carried out in all the cases using G Banding technique. Of the 141 patients studied, 17 patients showed secondary chromosomal alterations along with primary chromosomal alterations. In two patients of CML with secondary chromosomal alteration t(4:9:22), molecular cytogenetic technique (FISH) has been carried out which has confirmed the primary observations revealed by the conventional cytogenetic technique. Other secondary alterations were numerous and would have been missed if only FISH or PCR technique would have been used for diagnosis. We observed from our study that advanced molecular techniques like FISH and PCR cannot replace the conventional cytogenetic study but are useful as supportive and confirmative diagnostic tools.
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Aberraciones Cromosómicas , Cromosomas/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide/genética , Síndromes Mielodisplásicos/genética , Enfermedad Aguda , Bandeo Cromosómico , Deleción Cromosómica , Citogenética , Sondas de ADN , ADN de Neoplasias/genética , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/patología , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/patología , Translocación GenéticaRESUMEN
A Spanish man is diagnosed with a non-small cell lung cancer with pleural extension. A chemotherapy combining cisplatin and gemcitabine allows obtaining an excellent partial remission. A contralateral pleural effusion is noted in a context of weight loss and fever. The differential diagnosis of pleural effusion is discussed.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Derrame Pleural Maligno , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/tratamiento farmacológico , Derrame Pleural Maligno/etiologíaAsunto(s)
Crisis Blástica/genética , Genes abl , Haploidia , Antineoplásicos/uso terapéutico , Humanos , Hidroxiurea/uso terapéutico , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana EdadRESUMEN
The aim of this work was to develop a direct in situ reverse transcription polymerase chain reaction (in situ RT-PCR) assay for the detection of oestrogen receptor alpha (ERalpha) mRNA on in vitro cell lines and breast tumour cell smears. ERalpha mRNA amplification was performed on MCF-7 (ERalpha positive) and MDA-MB-231 (ERalpha negative) cell lines as well as on 51 cytological smears of breast tumour samples from patients. The in situ amplification of mRNA in cell lines and ex vivo breast tumours was successful. However, finding an equilibrium between optimal cell morphology and PCR performance varied with each tumour, leading to difficulty in standardisation for daily practice. Nonetheless, in situ RT-PCR is a useful tool for the detection of ERalpha mRNA in selected cases, both in vitro and ex vivo. J Clin PATHOL: Mol Pathol
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Neoplasias de la Mama/genética , ARN Mensajero/análisis , Receptores de Estrógenos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Fijación del Tejido/métodos , Células Tumorales CultivadasRESUMEN
Lymphoepithelioma-like carcinoma (LELC) of uterine cervix is an uncommon variant of squamous cell carcinoma (SCC). We report here 2 new cases in which DNA sequences from human papilloma virus (HPV) types 16 and 18 were detected by polymerase chain reaction (PCR). To the best of our knowledge, HPV infection has not been previously described in similar cases occuring in European women. Moreover, Epstein-Barr virus (EBV), which is frequently associated with cervical LELC in Asian women, was absent in our 2 cases. These results suggest that HPVs but not EBV can play a role in the pathogenesis of LELC occuring in women originating from Western countries.
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Carcinoma de Células Escamosas/patología , Papillomaviridae , Neoplasias del Cuello Uterino/patología , Carcinoma de Células Escamosas/virología , Cuello del Útero/patología , Cuello del Útero/virología , ADN Viral/genética , Femenino , Herpesvirus Humano 4/genética , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/virología , Neoplasias del Cuello Uterino/virologíaRESUMEN
Chromosomic aberrations play a major role in the initiation and the progression of benign as well as malignant tumors. In particular, trisomy 12 is frequently observed in female genitourinary tract tumors and constitutes a recurrent and often unique anomaly in stromal ovarian tumors such as fibrothecomas. Today, the genetic analysis of fresh or fixed solid tumors is enabled by the fluorescent in situ hybridization method (FISH). Using FISH and/or conventional cytogenetics, we analysed 12 ovarian stromal tumors (6 fibromas, 3 fibro thecomas and 3 thecomas). All of these tumors were benign and trisomy 12 was observed in all cases. Moreover, 3 cases presented trisomy and tetrasomy for chromosome 12 simultaneously. The high frequency of trisomy 12 in this tumor type suggests that this abnormality might be implicated in ovarian tumorigenesis.
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Cromosomas Humanos Par 12 , Hibridación Fluorescente in Situ , Neoplasias Ováricas/genética , Trisomía , Adulto , Anciano , Femenino , Fibroma/genética , Humanos , Cariotipificación , Persona de Mediana Edad , Neoplasia Tecoma/genéticaRESUMEN
To obtain an adequate cervical smear for making a correct cytologic diagnosis, smear taking, laboratory handling and interpretation must be optimal. Many people are involved, and only by a combined effort of all links can this target be seriously approached: the smear takers will have to be open minded about technical improvements and read the morphologic descriptions cautiously; in the laboratory, cytotechnicians and physicians will have to challenge themselves and each other. It is mandatory to discard specimens that do not meet general standards of adequacy. At present a host of new techniques are being implemented. It is not feasible for all laboratories to be engaged in testing these new methods, but we are all requested to follow the development the best we can and switch to new ways when justified. Our working conditions are very different; therefore, it is our professional responsibility and plight to respond at the right time. So far the conclusion is that the conventional Pap smear is the international standard of care for the diagnosis of cervical cancer precursers in cancer screening programs. Certainly, this may change within a very short time. Liquid-based techniques, and in particular HPV technologies, are just around the corner.
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Biología Celular/normas , Laboratorios/normas , Prueba de Papanicolaou , Manejo de Especímenes , Neoplasias del Cuello Uterino/patología , Frotis Vaginal/normas , Femenino , Humanos , Tamizaje Masivo , Control de CalidadRESUMEN
UNLABELLED: We retrospectively investigated 17 cases of primary and metastasizing Merkel cell carcinomas (MCC) from 14 patients using chromosomal in-situ hybridization (CISH) to study the occurrence of trisomy 6 in these lesions. METHODS AND RESULTS: Histological diagnosis on all tumour samples was obtained on haematoxylin and eosin stained sections. Immunohistochemistry was performed with antibodies against pancytokeratin (CAM 5.2), cytokeratin 20 (CK20), MIC2 antigen (CD99), neuron-specific enolase (NSE), and chromogranin A (chrA). Sections (4 microm) of the paraffin-embedded tumours were analysed with alpha-satellite centromeric probes for chromosome 6 or 17 using CISH. The signal was amplified by the Tyramide Signal Amplification (TSA) assay. Immunohistochemically, the tumours showed the same general epithelial neuro-endocrine pattern: 11/13 expressed cytokeratin 20, and 47% exhibited trisomy 6, with no significant difference between primary and metastatic lesions. Incomplete follow-up data did not allow us to establish a prognostic value of trisomy 6, however, this aberration might be an additional diagnostic tool in distinguishing MCC from other small round blue cell tumours. CONCLUSIONS: CISH seems to be a promising adjunctive method to diagnose Merkel cell carcinoma. Trisomy 6 should be investigated more closely in these cases, as has been done for chromosomes 1 and 11. Of particular interest would be identification of modifications in proto-oncogene(s) located on chromosome 6.
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Carcinoma de Células de Merkel/genética , Cromosomas Humanos Par 6 , Neoplasias Cutáneas/genética , Trisomía , Anciano , Anciano de 80 o más Años , Biomarcadores , Carcinoma de Células de Merkel/química , Carcinoma de Células de Merkel/secundario , Cromogranina A , Cromograninas/análisis , Citogenética , Femenino , Humanos , Hibridación Fluorescente in Situ , Proteínas de Filamentos Intermediarios/análisis , Queratina-20 , Queratinas/análisis , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/análisis , Proto-Oncogenes Mas , Neoplasias Cutáneas/química , Neoplasias Cutáneas/patologíaRESUMEN
We here report the clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data on 14 patients with a myeloid malignancy and structural aberration of chromosome band 11q23 associated with overrepresentation or amplification of the MLL gene. The number of copies of MLL varied from three (two cases) to a cluster consisting of multiple hybridization spots. Together with previous reports, available data indicate that amplification of 11q23/MLL is a recurrent genetic change in myeloid malignancy. It affects mainly elderly patients and is often associated with dysplastic bone marrow changes or with complex karyotypic aberrations, suggestive of genotoxic exposure. It is associated with a poor prognosis. In addition, FISH analysis of nine cases with additional 11q probes showed that the overrepresented chromosomal region is generally not restricted to MLL, and Southern blot analysis indicated that amplification does not involve a rearranged copy of this gene. The significance of MLL amplification and the mechanisms by which it could play a role in leukemogenesis and/or disease progression remain to be elucidated.
Asunto(s)
Cromosomas Humanos Par 11/genética , Proteínas de Unión al ADN/genética , Amplificación de Genes/genética , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Proto-Oncogenes , Factores de Transcripción , Adulto , Anciano , Anciano de 80 o más Años , Southern Blotting , Femenino , Dosificación de Gen , N-Metiltransferasa de Histona-Lisina , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mieloide/diagnóstico , Masculino , Persona de Mediana Edad , Proteína de la Leucemia Mieloide-Linfoide , Estudios RetrospectivosRESUMEN
Overexpression and amplification of the HER-2 oncogene in patients with breast cancer has correlated with early onset of metastasis, resistance to hormonal therapy and some forms of chemotherapy, and shortened survival. Therefore, evaluation of this putative prognostic or predictive factor seems critical. Because different antibodies are used for the detection of the 185-kd HER-2 oncoprotein, we studied the sensitivity of 3 frequently used antibodies. Immunohistochemistry results were correlated with gene amplification level as assessed by fluorescence in situ hybridization. Protein overexpression was found in 17.2% and 12.5% of cases using antibodies against the external (TAB250) and internal (CB11) domains of the protein, respectively, and in 38.0% of cases using a rabbit polyclonal antibody. Fluorescence in situ hybridization was successful in all 160 tumors, and amplification was found in 37 tumors (23.1%). The monoclonal antibody TAB250 had the lowest misclassification rate, 9.6% (sensitivity, 67%; specificity, 97.5%).
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Especificidad de Anticuerpos , Neoplasias de la Mama/química , Inmunohistoquímica , Receptor ErbB-2/análisis , Anticuerpos , Anticuerpos Monoclonales , Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Estudios Prospectivos , Receptor ErbB-2/genéticaRESUMEN
Hyperplastic lymphoid tissues of the Waldeyer's ring in human immunodeficiency virus (HIV)-infected patients may occasionally contain multinucleated giant cells (MGCs). These cells, which are unrelated to any opportunistic infection, previously have been demonstrated to harbor significant amounts of HIV. Studies undertaken to characterize these MGCs have generated conflicting results: some reports suggested a macrophage origin, whereas others supported a dendritic cell lineage. This study was performed to determine the occurrence of MGCs in a series of adenoid/tonsil specimens from HIV-seropositive patients showing no histological evidence of opportunistic infection in order to further characterize the phenotype of these cells and to investigate the role of a viral infection in their pathogenesis. Adenoid/tonsil tissue specimens from 21 HIV-seropositive patients with no documented opportunistic infection were scrutinized for the presence of MGCs and evaluated immunohistochemically on paraffin sections by antibodies directed against various macrophage and DC antigens. These antigens included CD68, the macrophage marker 3A5, major histocompatibility complex Class II, S-100 protein, CD1a, and CD83. Additional immunostainings directed at CD21 and CD35 as well as at the HIV-associated p24 antigen were also performed. Finally, the presence of Epstein-Barr virus and human herpesvirus 8 viral sequences was investigated by in situ hybridization and by polymerase chain reaction analysis, respectively. MGCs were found in 14 patients (66.7%), regardless of gender, age, method of viral transmission, CD4 cell count, viral load, or ethnic group. These cells were mostly localized at the lymphoepithelium layer of the tonsillar crypts and, to a lesser extent, in the interfollicular areas of the underlying lymphoid tissue, which consistently exhibited features of follicular hyperplasia. Phenotypically, MGCs were found to be CD68+, 3A5+, major histocompatibility complex Class II+, S-100 protein+/-, CD1a-, CD21-, CD35-, and CD83-. Although the HIV-associated p24 protein was consistently present in the cytoplasm of these cells, no sign of Epstein-Barr virus or human herpesvirus 8 infection could be demonstrated. Consequently, our study didn't show any conclusive evidence to support that MGCs in hyperplastic lymphoid tissues of the Waldeyer's ring from HIV-seropositive patients originated from dendritic cells. The definite nature of these cells has yet to be elucidated, but it is plausible that they simply represent activated macrophages that are infected with HIV present in the oropharyngeal secretions during the circulation of their precursor through the lymphoepithelium area of adenoids and tonsils.