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1.
Breast Cancer Res Treat ; 133(3): 969-77, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22108781

RESUMO

We have previously showed the presence of the simian virus 40 (SV40) and the mouse mammary tumor virus (MMTV)-like in a significant proportions of Tunisian breast carcinomas. However, to date there are no published studies concerning evaluation of the possible implication of the human polyomaviruses JC (JCV) and BK (BKV) in breast carcinomas. The presence of JCV and BKV DNA was investigated by PCR in a 123 primary breast carcinomas and matched adjacent non-tumor breast tissues. The results were correlated to clinicopathological and virological parameters. JCV T-antigen DNA was detected in 23% of breast carcinoma cases; however, all cases were negative for BKV. JCV T antigen PCR products were further confirmed as authentic JCV genome by direct sequencing. JCV was found in invasive ductal carcinomas (28/112 cases) but not in invasive lobular carcinomas (0/5) or medullary carcinomas (0/6). JCV DNA presence correlates inversely with the expression of estrogen (P = 0.022) and progesterone (P = 0.008) receptors. JCV DNA presence correlates also with "triple negative" phenotype (P = 0.021). With regard to virological data, a trend toward an inverse correlation was noted between the presence of JCV and SV40 (P = 0.06). Moreover, significant correlation was found between multiple viral infection (JCV, and/or SV40, and/or MMTV-like in the same tumor) and "triple negative" phenotype (P = 0.001) and also with p53 accumulation (P = 0.028). To the best of our knowledge, this is the first study demonstrating the presence of JCV in a subset of breast carcinomas. Also our results suggest that "triple negative" breast carcinomas are viral-related tumors.


Assuntos
Vírus BK/genética , Neoplasias da Mama/virologia , Carcinoma/virologia , Vírus JC/genética , Adulto , Idoso , Vírus BK/metabolismo , Sequência de Bases , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Carcinoma/diagnóstico , Carcinoma/mortalidade , Transformação Celular Viral/genética , DNA Viral , Feminino , Humanos , Vírus JC/metabolismo , Pessoa de Meia-Idade , Dados de Sequência Molecular , Estadiamento de Neoplasias , Alinhamento de Sequência , Tunísia , Adulto Jovem
2.
Ann Biol Clin (Paris) ; 69(2): 167-73, 2011.
Artigo em Francês | MEDLINE | ID: mdl-21464009

RESUMO

Hereditary non-polyposis colorectal cancer (HNPCC) is associated in more than 95% to a germline mutation in the genes of the mismatch repair (MMR) of DNA. The aim of this study was to assess the utility of immunohistochemistry, a simple and fast technique, in the triage of families where HNPCC is suspected. Tumor samples included in this study were from patients with resection for colorectal cancer, examined in our laboratory between 2004 and 2007. For each case, a formalin-fixed paraffin-embedded tissue block containing tumor tissue and normal adjacent mucosa was selected. Tumor specimens were examined with immunohistochemistry for the presence of hMLH1, hMSH2, and hMSH6 proteins. Scoring of the tumor staining was performed without any knowledge of patients' family history. The loss of protein expression was noted in four patients among 48 cases tested: two cases with isolated loss of hMSH2, a case with isolated loss of hMSH6 and one case with combined loss of MSH2/MSH6. No case has shown a suppression of hMLH1 protein. Comparing the immunohistochemical results for clinical has revealed a clear correlation between loss of protein expression demonstrated by immunohistochemistry and clinical data. Indeed, three cases among the four who showed no expression of MMR proteins showed at least one clinical criterion predictive of HNPCC. In conclusion, our study support the potential utility of immunohistochemistry to identify a significant portion of colorectal tumors derived from germline mutation of MMR genes and can be used as an adjunct measure in the identification of HNPCC.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA , DNA de Neoplasias/genética , Imuno-Histoquímica , Adulto , Humanos , Pessoa de Meia-Idade
3.
Int J Cancer ; 127(11): 2669-77, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20521249

RESUMO

In this article, we analyzed trends in incidence rates of the major cancer sites for a 14-year period, 1993-2006, in the Sousse region localized in the centre of Tunisia. Five-year age-specific rates, crude incidence rates (CR), world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual data on population size and its estimated age structure. A total of 6,975 incident cases of cancer were registered, with a male to-female sex ratio of 1.4:1. ASRs showed stable trends (-0.1% in males, and +1.0% in females). The leading cancer sites in rank were lung, breast, lymphoma, colon-rectum, bladder, prostate, leukemia, stomach and cervix uteri. For males, the incidence rates of lung, bladder and prostate cancers remained stable over time. While, cancers of colon-rectum showed a marked increase in incidence (APC: +4.8%; 95% CI: 1.2%, 8.4%) and non-Hodgkin's lymphoma (NHL) showed a notable decline (APC: -4.4%; 95% CI: -8.2, -0.6). For females, cancers of the breast (APC: +2.2%; 95% CI: 0.4%, 4.0%) and corpus uteri (APC: +7.4%; 95% CI: 2.8%, 12.0%) showed a marked increase in incidence during the study period, while the cervix uteri cancer decreased significantly (APC: -6.1%; 95% CI: -9.2%, -3.0%). The results underline the increasing importance of cancer as a cause of mortality and morbidity in Tunisia. Our findings justify the need to develop effective program aiming at the control and prevention of the spread of cancer amongst Tunisian population.


Assuntos
Neoplasias/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Tunísia/epidemiologia , Adulto Jovem
4.
Cancer Sci ; 101(7): 1722-30, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20398054

RESUMO

Diffuse large B-cell lymphomas (DLBCL) are the most common type of aggressive lymphomas, with considerable heterogeneity in clinical presentation, molecular characteristics, and outcome. Previous studies have showed significant correlations between DNA methyltransferase (DNMT) overexpression and unfavorable prognosis in human cancers. Therefore, we investigated in this study the biological and prognostic significance of DNMT1, DNMT3a, and DNMT3b protein expression in DLBCL. DNA methyltransferase (DNMT) expression was analyzed by immunohistochemistry in 81 DLBCL cases and correlated with clinicopathological parameters. Kaplan-Meier curves were used to estimate survival rates, and the Cox proportional hazard regression model was used to evaluate the prognostic impact of DNMT expression. Our results showed that overexpression of DNMT1, DNMT3a, and DNMT3b were detected in 48%, 13%, and 45% of investigated cases, respectively. DNA methyltransferase 1 (DNMT1) and DNMT3b overexpression was significantly correlated with advanced clinical stages (P = 0.028 and P = 0.016, respectively). Moreover, concomitant expression of DNMT1 and DNMT3b was significantly correlated with resistance to treatment (P = 0.015). With regard to survival rates, although data was available only for 40 patients, DNMT3b overexpression was significantly correlated with shorter overall survival (P = 0.006) and progression-free survival (P = 0.016). Interestingly, multivariate analysis demonstrated that DNMT3b overexpression was an independent prognostic factor for predicting shortened overall survival (P = 0.004) and progression-free survival (P = 0.024). In conclusion, DNMT3b overexpression was identified as an independent prognostic factor for predicting shortened survival of patients with DLBCL and could be, therefore, useful in identifying patients who would benefit from aggressive therapy.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Linfoma de Células B/genética , Idoso , DNA (Citosina-5-)-Metiltransferase 1 , DNA Metiltransferase 3A , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Linfoma de Células B/diagnóstico , Linfoma de Células B/enzimologia , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , DNA Metiltransferase 3B
5.
Mod Pathol ; 23(4): 522-30, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20081806

RESUMO

JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.


Assuntos
Metilação de DNA , Genes Supressores de Tumor , Infecções por Polyomavirus/complicações , Neoplasias Gástricas/virologia , Infecções Tumorais por Vírus/complicações , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais de Tumores/isolamento & purificação , Feminino , Humanos , Imuno-Histoquímica , Vírus JC/imunologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
6.
Ann Biol Clin (Paris) ; 68(3): 297-303, 2010.
Artigo em Francês | MEDLINE | ID: mdl-20478773

RESUMO

OBJECTIVES: To investigate the distribution of HPV genotypes inuterine cervical lesions in Central Tunisia in order to predict the impact ofHPV vaccines and HPV-based screening tests among Tunisian women. MATERIAL AND METHODS: We performed a retrospective study of 146 fixed tissues including 30 benign lesions, 36 low-grade cervical intraepithelial neoplasias (CIN1), 45 high-grade cervical intraepithelial neoplasias (CIN2/3), 26 invasive squamous cell carcinomas (SCC) and 9 adenocarcinomas. HPV infection detection and typing were investigated by PCR technique using consensus GP5/GP6 primers and type specific primers for HPV6/11, 16, 18, 31 and 33. RESULTS: Among our patients, overall HPV prevalence was 73.6% (p = 0.0001). HPV infection was associated to 84% of precancerous lesions and 83.9% of cancers. High-risk HPV infection (HPV16 and 18) was detected in 17.4% of CIN1, 74.3% of CIN2/3 (p = 0.002) and 73.1% of cancers (p = 0.001). HPV16 was the most common type among CIN2/3 (51.2%, p < 0.001), invasive SCC (47.6%, p = 0.001) and adenocarcinomas (80%, p < 0.001). CONCLUSION: This study supports previous population-based studies in which similar HPV detection rates were found among random samples of women. HPV-based screening tests and HPV vaccination would be efficient in uterine cervix cancer prevention among women in the Central Tunisia.


Assuntos
Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/virologia , Carcinoma/epidemiologia , Carcinoma/virologia , DNA Viral/isolamento & purificação , Feminino , Humanos , Infecções por Papillomavirus/genética , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/virologia , Prevalência , Estudos Retrospectivos , Tunísia , Neoplasias do Colo do Útero/epidemiologia
7.
Eur Arch Otorhinolaryngol ; 266(5): 763-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18560865

RESUMO

Inflammatory myofibroblastic tumor (IMT) is a rare entity. It is usually found in the lung and upper respiratory tract. Its location in the thyroid is exceedingly rare. Only seven cases of IMT of the thyroid were reported in the literature, mostly after the age of 50 years. The predominant histological pattern in all previously reported cases is that of marked plasma cell infiltrate. We report the detailed clinico-pathological and immunophenotypical features of a case of IMT of the thyroid in an 18-year-old girl with a family history of goiter. Our case is unique because it is the first and only known case of IMT of the thyroid in its alternative sclerosing subtype.


Assuntos
Neoplasias de Tecido Muscular/complicações , Neoplasias de Tecido Muscular/patologia , Esclerose/complicações , Esclerose/patologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Adolescente , Feminino , Humanos , Imuno-Histoquímica , Neoplasias de Tecido Muscular/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
8.
Tunis Med ; 87(2): 127-32, 2009 Feb.
Artigo em Francês | MEDLINE | ID: mdl-19522446

RESUMO

BACKGROUND: The lethal osteochondrodysplasias are rare, their prevalence is estimated at 1 per 10 000 births. Mostly have genetic determinism. AIMS: To describe the malformations and dysmorphic features in lethal osteochondrodysplasias METHODS: Our study involved 32 cases of lethal fetal Osteochondrodysplasias, collected over a period of 14 years in the pathological department of Sousse. RESULTS: Our series consisted of 23 foetuses from a medical termination of pregnancy, 6 newborns and 3 stillbirths. The mean age of mothers was 28 years old, consanguinity was observed in 61%. 3 cases of recurrence of the disease in three families were noted. The bone abnormalities were detected in antenatal ultrasonography in 25 cases (87%) and at birth in 7 cases. Ultrasound showed micromelia in all cases, a narrow chest in 5 cases and spina bifida in 3 cases. The feto-pathological exam, including a macroscopic examination, radiological and histological samples of bone, has allowed us, based on the International Classification of 2001 to classify the 32 cases of Osteochondrodysplasias in: 8 cases of Achondrogenesis type I (type Parenti-Fraccaro), 3 cases of Achondrogenesis type II (Langer Saldino), 9 cases of lethal osteogenesis imperfecta, 8 cases of thanatophoric dysplasia, 4 cases of Schneckenbecken dysplasia, 2 cases of Short rib polydactyly syndrome, Majewski type and 1 case of asphyxiating thoracic dysplasia.


Assuntos
Anormalidades Múltiplas/patologia , Osteocondrodisplasias/patologia , Ultrassonografia Pré-Natal , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/mortalidade , Aborto Legal/estatística & dados numéricos , Adulto , Autopsia , Consanguinidade , Feminino , Doenças Fetais/patologia , Humanos , Incidência , Recém-Nascido , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Osteocondrodisplasias/mortalidade , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Disrafismo Espinal/patologia , Natimorto , Tórax/anormalidades , Tunísia/epidemiologia
9.
Oral Oncol ; 44(8): 775-83, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18206419

RESUMO

Tunisia is one of the world's intermediate risk areas for nasopharyngeal carcinoma (NPC). Loss of heterozygosity (LOH) on the short arm of chromosome 3 (3p) is the most frequent genetic change reported in NPC from endemic areas. In the present study, we investigate the incidence of LOH and microsatellite instability (MSI) on chromosome 3p in 49 microdissected primary NPC specimens and corresponding non-cancerous tissues from Tunisian patients using six microsatellite polymorphic markers. LOH at one or more markers was observed in 40 out of 48 informative cases (83.3%). The markers D3S1038 at 3p25.2-26.1 and D3S1076 at 3p21.1-21.2 have showed the highest frequency of LOH (51.3%), followed by D3S1067 at 3p14.3-21.1 (48.7%), D3S1568 at 3p21.3 (47.4%), D3S659 at 3p13 (15.3%), and D3S1228 at 3p14.1-14.2 (11%). Interestingly, MSI at one or more microsatellite markers was observed in 15 cases (31.2%). The highest frequency of MSI was presented by D3S1568 (18.4%), D3S1067 (17.9%), and D3S1038 (12.8%). With regard to clinicopathological features, LOH was found to be less common in young patients (under 25 years) than in adults (p=0.04), whereas MSI was found to be more frequent in patients under 45 years than in older patients (p=0.006). No significant correlation was found between LOH or MSI and the other clinicopathological features investigated including, gender, tumor size, lymph node metastasis, UICC clinical stage, and histological subtype. This study revealed different patterns of allelic imbalance on chromosome 3P in NPC between age groups in Tunisia, and suggests an alteration in the DNA mismatch repair machinery that may be, in part, responsible of the early age onset form of this disease in North African populations. More attention should be given to the mismatch repair system in the juvenile form of this disease in future studies.


Assuntos
Desequilíbrio Alélico/genética , Carcinoma de Células Escamosas/genética , Cromossomos Humanos Par 3/genética , Perda de Heterozigosidade/genética , Instabilidade de Microssatélites , Neoplasias Nasofaríngeas/genética , Adolescente , Adulto , Idoso , Transformação Celular Neoplásica/genética , Criança , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Tunísia , Adulto Jovem
10.
Dermatol Online J ; 14(8): 11, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19061571

RESUMO

BACKGROUND: Malignant proliferating trichilemmal tumor is a rare skin tumor that affects mainly older women. It mimicks differential squamous cell carcinoma and its biological behavior is unpredictable. OBJECTIVE: To report on a new case of malignant proliferating trichilemmal tumor of the scalp and to describe the clinical and histopathologic findings. METHODS: A tumor measuring 2 cm was surgically excised with a 0.5 cm conservative margin of normal tissue RESULTS: Based on the histopathologic findings of tumor, this case was diagnosed as proliferating trichilemmal tumor of the scalp. Eleven months after tumor resection, the patient is free of disease. CONCLUSION: Malignant proliferating trichilemmal tumor is a rare malignant lesion with an unpredictable biological behavior. After wide excision, long term clinical follow up of the patient for early diagnosis of metastases is judicious.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasia de Células Basais/diagnóstico , Couro Cabeludo/patologia , Neoplasias Cutâneas/diagnóstico , Idoso , Carcinoma/diagnóstico , Divisão Celular , Diagnóstico Diferencial , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Queratinócitos/patologia , Neoplasia de Células Basais/patologia , Neoplasia de Células Basais/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
11.
Tunis Med ; 86(9): 816-20, 2008 Sep.
Artigo em Francês | MEDLINE | ID: mdl-19472782

RESUMO

BACKGROUND: Holoprosencephaly (HPE) is a rare and serious brain anomaly of heterogeneous aetiology. AIMS: description of neuropathologic patterns of HPE to eventually integrate it into recognized syndrome METHODS: The authors report 15 cases of HPE, examined at the department of pathology of Sousse (Tunisia) over a period of 11 years. RESULTS: The average age of mothers was 32 years and 46% of them were primigestes. The rate of consanguinity was 45%. The population of the study was formed of 13 foeti, 12 of which arose from a medical interruption of pregnancy, and 2 newborns. The average foetal age was of 25,5 weeks of gestation. Antenatal diagnosis was performed on ultrasounds signs represented by a hydrocephalus (7 cases), a microcephaly (4 cases), a harmonious delay of growth (3cas) and a facial dysmorphy (38%) dominated by cyclopia. Neuropathologic Exam identified 13 cases of alobair HPE and 2 cases semi lobar. The HPE was isolated in 2 cases with an unknown caryotype, it was syndromic in 13 cases, associated with a chromosome abnormality confirmed in 3 observations. CONCLUSION: The neonatal outcome of this deformation remains very poor justifying the interruption of pregnancy except in the lobar forms. An exhaustive domestic inquiry is compulsory to propose to parents a most adequate genetic counselling.


Assuntos
Feto/patologia , Holoprosencefalia/patologia , Adulto , Feminino , Humanos , Estudos Retrospectivos , Adulto Jovem
12.
Tunis Med ; 86(7): 636-42, 2008 Jul.
Artigo em Francês | MEDLINE | ID: mdl-19472723

RESUMO

AIM: Analyze epidemiological and evolutive profile of paediatric celiac disease in the region of Sousse. METHODS: We studied retrospectively 80 cases enrolled in the paediatrics' department of Sousse between 1993 and 2003. RESULTS: There were 44 girls and 36 boys (sex-ratio=0.81). The middle age of gluten introduction was 9 months, with extremes going from 1 to 24 months. Free interval between the introduction of gluten and the beginning of the symptoms was meaningfully more elevated in patients who received gluten after the age of 6 months (p=0.036). At the time of the diagnosis, the middle age of our patients was six years with extremes going from nine months to 17 years. The classic form of celiac disease with chronic diarrhoea has been observed in 85% of the cases. The morbid associations with celiac disease were dominated by the diabetes type 1 noted in 5% of the cases. Antigliadin antibodies, practiced in first intension, were positive in 98.6%. At histology, villous atrophy was sub-total to total in 96.25% of the cases and partial in 3.75% of the cases. Follow-up was on average at 18 months. Adhesion to the gluten-free diet (GFD) was judged satisfactory in 81.45% of the cases on average. Catch up growth, although remarkable, was not very satisfactory. Indeed, several patients adhering little or not to the GFD kept, at one year of evolution, a ponderal and stature delay superior to 2SD.


Assuntos
Doença Celíaca/dietoterapia , Doença Celíaca/epidemiologia , Adolescente , Anticorpos/análise , Doença Celíaca/diagnóstico , Criança , Pré-Escolar , Dieta Livre de Glúten , Feminino , Gliadina/imunologia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Tunísia/epidemiologia
13.
Tunis Med ; 86(4): 383-5, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19476144

RESUMO

We report a rare case of intradural immature teratoma in 2-year-old girl, interesting conus medullaris to sacrum, worsening neurological deficits. The neoplasm discovered by magnetic resonance imaging, was completely resected. We describe the clinical, radiological and pathological findings of this tumor with a review of the Literature and we insist in the difficulty of treatment.


Assuntos
Neoplasias da Coluna Vertebral , Teratoma , Pré-Escolar , Feminino , Humanos , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/cirurgia , Teratoma/diagnóstico , Teratoma/cirurgia
14.
Int J Cancer ; 121(12): 2693-702, 2007 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17724719

RESUMO

The simian virus SV40 (SV40), a potent DNA oncogenic polyomavirus, has been detected in several human tumors including lymphomas, mainly in diffuse large B-cell type (DLBCL). However, a causative role for this virus has not been convincingly established. Hypermethylation in promoter regions is a frequent process of silencing tumor suppressor genes (TSGs) in cancers, which may be induced by oncogenic viruses. In this study, we investigated the relationship between the presence of SV40 DNA sequences and the methylation status of 13 TSGs in 108 DLBCLs and 60 nontumoral samples from Tunisia. SV40 DNA presence was investigated by PCR assays targeting the large T-antigen, the regulatory and the VP1 regions. Hypermethylation was carried out by methylation-specific PCR. SV40 DNA was detected in 63/108 (56%) of DLBCL and in 4/60 (6%) of nontumoral samples. Hypermethylation frequencies for the tested TSGs were 74% for DAPK, 70% for CDH1, SHP1, and GSTP1, 58% for p16, 54% for APC, 50% for p14, 39% for p15, 19% for RB1, 15% for BLU, 3% for p53, and 0% for p300 and MGMT. No hypermethylation was observed in nontumoral samples. Hypermethylation of SHP1, DAPK, CDH1, GSTP1 and p16 genes were significantly higher in SV40-positive than in SV40-negative DLBCL samples (p values ranging from 0.0006 to <0.0001). Our findings showed a high prevalence of SV40 DNA in DLBCLs in Tunisia. The significant association of promoter hypermethylation of multiple TSGs with the presence of SV40 DNA in DLBCLs supports a functional effect of the virus in those lymphomas.


Assuntos
Metilação de DNA , Inativação Gênica , Genes Supressores de Tumor , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/virologia , Regiões Promotoras Genéticas , Vírus 40 dos Símios , Proteínas Supressoras de Tumor/genética , Apoptose/genética , Adesão Celular/genética , Ciclo Celular/genética , Diferenciação Celular/genética , Reparo do DNA/genética , DNA Viral , Eletroforese em Gel de Ágar , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/patologia , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Tunísia
15.
Leuk Lymphoma ; 48(7): 1323-31, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17613761

RESUMO

The association between Epstein-Barr virus (EBV) and classical Hodgkin's lymphoma (cHL) varies according to the geographic location. In this work we sought to characterize EBV involvement in a series of 111 cHL cases diagnosed in Belgium. The overall prevalence of EBV infection detected by in situ hybridization in Reed-Sternberg cells was 33%. EBV positivity correlated with older age at diagnosis (>54 years; p = 0.01), mixed cellularity subtype (p = 0.000001), male gender (p = 0.004) and tended to be associated with higher clinical stage (III/IV; p = 0.02). The molecular features of the virus in EBV-positive cHL were studied by comparison with a series of reactive tonsils. A 30-bp deletion within the LMP-1 gene was in 15/28 (53.6%) EBV-positive cHL cases, and in 41.7% of reactive tonsil samples. This variant did not correlate with any clinical or pathological feature. The EBV strain was type A in all cHL and reactive samples.


Assuntos
Herpesvirus Humano 4/genética , Doença de Hodgkin/virologia , Proteínas da Matriz Viral/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Criança , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Doença de Hodgkin/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tonsila Palatina/virologia , Prevalência , Células de Reed-Sternberg/virologia , Fatores de Risco , Deleção de Sequência
16.
Virchows Arch ; 449(2): 220-4, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16673118

RESUMO

CD10 is a cell surface zinc metalloprotease expressed through a variety of normal cell types, including lymphoid precursor cells, germinal center B lymphocytes, and some epithelial cells. Many studies showed that CD10 expression is associated with the tumor progression of a large variety of cancers, such as breast and colorectal carcinomas. The aim of this study was to investigate the expression of CD10 in nasopharyngeal carcinoma (NPC). The expression of CD10 was immunohistochemically examined in 47 paraffin embedded NPC biopsies from Tunisian patients compared with 16 reactional nasopharyngeal mucosas. A significant expression of CD10 was observed in stromal fusiform cells in 46.8% of NPC cases but was not in malignant and normal epithelial cells. There was no significant expression of CD10 in control group. The stromal expression of CD10 was more frequently detected in advanced clinical stage than early stage (56 vs 23%; p=0.04) and in patients older than 25 years than in patients under 25 years (56.2 vs 26.5%; p=0.05). Our study is the first in investigating CD10 expression in nasopharyngeal carcinoma and showed that CD10 expression by stromal cells in this malignancy play an important role in tumor progression, particularly in older patients.


Assuntos
Neoplasias Nasofaríngeas/química , Neprilisina/análise , Adolescente , Adulto , Idoso , Criança , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Células Estromais/química
17.
Virchows Arch ; 448(5): 597-603, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16496173

RESUMO

Human papillomaviruses (HPVs) are causally involved in the genesis of cervical carcinomas and their precursors, and there is a strong relationship between the cyclin-dependant kinase inhibitor p16INK4A and HPV infection. This study was carried out to assess the correlations between p16INK4A expression as an early biomarker of the endocervical adenocarcinoma and HPV infection. p16INK4A expression and HPV typing were performed on 46 samples including 5 normal endocervix, 9 benign lesions of the endocervix, 25 endocervical adenocarcinomas, and 7 endometrioid adenocarcinomas of the uterine corpus. A semiquantification of the p16INK4A immunostaining was realized (using both the staining intensity and the percentage of positive cells) and was graded from 0 to 15. All of the 25 endocervical adenocarcinomas overexpressed p16INK4A; the adjacent epithelium and the connective tissue were strictly negative. No p16INK4A was detected in nine benign endocervical lesions and in five normal endocervix. Few endometrioid adenocarcinomas of the uterine corpus that infiltrate the endocervix exhibited a low immunoreactivity (score 0/15 or 1/15). This pattern of expression is significantly associated with HPV infection (p<10(-3)), mainly high-risk HPV types (p=0.02). Our results suggest that p16INK4A is a putative molecular biomarker that consistently discriminates uterine cervix adenocarcinomas from benign lesions and from endometrioid adenocarcinomas of the uterine corpus.


Assuntos
Adenocarcinoma/virologia , Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Neoplasias do Colo do Útero/virologia , Adenocarcinoma/metabolismo , Adulto , Feminino , Humanos , Imuno-Histoquímica , Infecções por Papillomavirus/metabolismo , Infecções Tumorais por Vírus/metabolismo , Neoplasias do Colo do Útero/metabolismo
18.
Pathol Res Pract ; 202(6): 425-31, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16677778

RESUMO

Polymerase chain reaction (PCR)-based analysis, employed for detecting immunoglobulin heavy chain (IgH) gene rearrangements, has become a diagnostic tool widely used in the investigation of B-cell lymphomas, but the overall sensitivity of these methods does not exceed 80%, notably in germinal center (GC) and post-GC B-cell origin lymphomas. Many PCR strategies devised for detecting immunoglobulin light chain (IgL) gene rearrangements have been developed to enhance the clonality detection rates. However, the feasibility of these methods in routine clinical diagnosis using paraffin-embedded tissues has not yet been investigated sufficiently. We studied a large series of 108 cases of B-cell lymphomas, as well as 20 reactive lymphoid tissues using degenerate primers to amplify immunoglobulin kappa (Igkappa) and lambda (Iglambda) light chain genes. B-cell clonality was further investigated using semi-nested PCR for IgH gene rearrangements. B-cell clonality was detected in 74%, 56.5%, and 43.5% of cases using IgH, Igkappa, and Iglambda PCR, respectively. By combining these methods, the clonality detection rate increased to 93.5%. Only polyclonal patterns were noted in reactive lymphoid samples. We concluded that in addition to the established methods for IgH analysis, a PCR-based approach for IgL gene rearrangements analysis improves the clonality detection rate in over 90% of B-cell lymphoma cases using routine histological specimens with poor preservation of the genomic DNA.


Assuntos
Rearranjo Gênico de Cadeia Leve de Linfócito B , Genes de Cadeia Leve de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/genética , Cadeias lambda de Imunoglobulina/genética , Linfoma de Células B/genética , Células Clonais/imunologia , Primers do DNA/química , Genes de Imunoglobulinas , Humanos , Inclusão em Parafina , Reação em Cadeia da Polimerase
19.
Tunis Med ; 84(9): 585-8, 2006 Sep.
Artigo em Francês | MEDLINE | ID: mdl-17263209

RESUMO

The solitary fibrous tumor (SFT), is an unusual entity, first described in the pleura, but can involve other serosal surfaces and viscera. We report two cases of extra-thoracic SFT involving the retro-peritoneum and the upper arm. Extra-thoracic TFS is a rarily wide morphologic and evolutive spectrum.


Assuntos
Neoplasias de Tecido Fibroso/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Extremidade Superior/patologia
20.
Tunis Med ; 84(6): 353-7, 2006 Jun.
Artigo em Francês | MEDLINE | ID: mdl-17042208

RESUMO

Our retrospective study was performed on 10 cases of granulomatous mastitis registered in Obstetric Gynaecology Department and Pathology Department of CHU F. Hached, Sousse, during 8 years period. The mean age was 36.4 years (range 32-59). Among these 10 cases. 8 were observed in reproductive-age women and 2 were noted in menopausal women. Clinical findings showed unilateral breast nodule associated with inflammatory signs in 4 cases, mammelonary retraction in 2 cases and serous or sero-purulent mamelonnary flow in 4 cases. Mamnmographic examination suggested a malignant tumor in 5 patients. In all cases, the diagnosis is made by histopathology. Surgical treatment consisted in wide excision with drainage or radical mastectomy, eventually with combination with antibiotic therapy and non steroid anti-inflammatory drugs. Prognostic features showed a good cicatrization in 4 cases, local recurrence and cutaneous fistulization in one patient. Granulomatous mastitis aetiology is still unclear, auto-immune aetio-pathogenesis appears more interesting and should be clarified.


Assuntos
Mastite , Adulto , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Mama/patologia , Diagnóstico Diferencial , Drenagem , Feminino , Humanos , Mamografia , Mastectomia Radical , Mastite/diagnóstico , Mastite/diagnóstico por imagem , Mastite/patologia , Mastite/cirurgia , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos
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