RESUMEN
The biliary system is an uncommon location for neuroendocrine tumours (NETs), and within this system, the common hepatic duct is an even more rare site for NETs. Clinical and radiological presentations are challenging because these tumours may be preoperatively confused with Klatskin-like lesions. Here we report a well-differentiated grade 2 NET arising from the common hepatic duct in a 64-year-old female. Curative surgery was performed, and no evidence of recurrent disease was observed at the 2-months follow-up.
Asunto(s)
Neoplasias de los Conductos Biliares , Procedimientos Quirúrgicos del Sistema Biliar/métodos , Antígeno Ki-67/análisis , Tumor de Klatskin/diagnóstico , Tumores Neuroendocrinos , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Diagnóstico Diferencial , Femenino , Conducto Hepático Común/diagnóstico por imagen , Conducto Hepático Común/patología , Conducto Hepático Común/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: About 10% to 15% of sporadic colorectal cancers demonstrate high level of microsatellite instability that is generally associated with aberrant methylation of hMLH1 promoter. AIM: To investigate the association between MSI status, hMLH1 protein expression and methylation status of the hMLH1 promoter in a cohort of Tunisian sporadic colorectal cancer. METHODS: Expression of MLH1 and MSH2 was determined by immunohistochemistry and the MSI status was analysed by microfluid-based on-chip electrophoresis. Methylation of the hMLH1 gene promoter was determined by methylation-specific PCR. RESULTS: Of the 150 colorectal cancers 57% were MSS, 28% were MSI-L and 15%were MSI-H. MSI-H tumors were more frequently right-sided, exhibited a stage III of TNM and tended more to be mucinous. The MSI status had no effect on overall patient survival. Most of the MSS/MSI-L 79% cancers were unmethylated at the hMLH1 promoter, while 26% MSI-H cancers were unmethylated. 84% of MSS and MSI-L expressed MLH1 and 52% of MSI-H expressed MLH1. Of the methylated MSI-H cases, 35% expressed MLH1 protein while 100% of the unmethylated MSI-H were positive for MLH1 staining. Of 11 MSI-H cancers with loss of MLH1 expression, all cases were also methylated while 50% MSI-H cancers with positive immunostaining for MLH1 were methylated at the hMLH1 promoter. CONCLUSION: Our study showed that MSI-H phenotype was mucinous, right-side and exhibit stade III of TNM. The relative correlation of MLH1 expression and promotor hypermethylation of hMLH1 for the MSI status is similar to that reported for several study.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Inestabilidad de Microsatélites , Proteínas Nucleares/genética , Regiones Promotoras Genéticas/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Estudios Retrospectivos , TúnezRESUMEN
The ß-galactoside-binding protein galectin-3 (gal-3) has pleitropic biological functions and has been implicated in cell growth, differentiation, adhesion, RNA processing, apoptosis, and malignant transformation. To investigate the pattern of inactivation of the gal-3 gene (LGALS3) in colorectal cancers (CRC), we studied a series of Tunisian patients with CRC to identify abnormal methylation in LGALS3 promoter using a methylation-specific PCR. We also examined the gal-3 gene expression by reverse transcription-PCR and the expression of gal-3 protein by immunohistochemistry. Analysis of DNA methylation in nonmucinous colorectal carcinomas expressing gal-3 protein showed an unmethylated profile of LGALS3 promoter, whereas gal-3 was aberrantly methylated in mucinous colorectal carcinomas. Complete loss of the gal-3 expression both at mRNA and the protein level was associated with the gal-3 methylation in the mucinous colorectal carcinomas. Our results show that methylation of the gal-3 promoter could be an important mechanism in the regulation of the expression of this gene in mucinous CRCs.
Asunto(s)
Adenocarcinoma Mucinoso/metabolismo , Colon/metabolismo , Neoplasias Colorrectales/metabolismo , Galectina 3/metabolismo , Regulación Neoplásica de la Expresión Génica , Región de Flanqueo 5'/genética , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patología , Colon/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Islas de CpG/genética , Metilación de ADN , Galectina 3/genética , Inmunohistoquímica , Regiones Promotoras Genéticas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TúnezRESUMEN
We examined the association of one linked GC/AT polymorphism at p73 with the risk of colorectal cancer. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. The p73 genotypes were determined by PCR-restriction fragment length polymorphism in 150 Tunisians patients with colorectal cancer and in 204 healthy control subjects. Immunohistochemistry was performed on normal mucosa, primary tumour and metastasis. The frequencies of the genotypes were 52% for wild-type (GC/GC), 31% for heterozygotes (GC/AT) and 17% for variants (AT/AT) in patients, and 54%, 35% and 11% in controls, respectively. There were no significant differences of the frequencies of the three genotypes between the patients and controls (p = 0.11). We did not find any relationship of the genotypes with clinicopathological features of patients. We found that patients with the AT/AT genotype had a significantly worse clinical outcome than those with the GC/AT and GC/GC genotype. There were no significant differences between tumoural immunostaining of the total p73 and p73 polymorphism (p = 0.16). However, we found a significant difference between the expression profile of DeltaNp73 isoform and frequencies of the three genotypes (p = 0.0001). No LOH was observed at p73 locus. Our results suggest that the AT/AT genotype is significantly associated with poor prognosis in colorectal cancer. All these findings suggest that p73 polymorphism analysis may provide useful prognostic information for colorectal cancer patients.
Asunto(s)
Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Supresoras de Tumor/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Estudios de Casos y Controles , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Exones , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Pérdida de Heterocigocidad , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Retrospectivos , Factores de Riesgo , Proteína Tumoral p73 , TúnezRESUMEN
BACKGROUND: Colorectal carcinoma is one of the main causes of cancer death in the worldwide with a decrease survival rate in relationship with a later diagnosis of advanced disease. AIMS: This study highlights the particular epidemiological, clinicopathological and immunohistochemical colorectal cancer profile. Indeed, our results differ markedly from that reported in the literature. METHODS: We underwent a retro and prospective study interesting 196 patients with colorectal carcinoma diagnosed in the pathological and cytological laboratory of Mongi Slim Hospital (Tunisia). Age at diagnosis, mode of presentation, sex, tumour location, macroscopic and histological features, TNM and Astler Coller stage were assessed and evaluated. RESULTS: We report here a particular epidemiological pattern which is characterised by younger age of the patients, equally distribution between men and women, predominant sporadic carcinomas and preponderance of rectosigmoid location. The poorer degree of differentiation and mucinous subtype are correlated with an advanced stage. It is also correlated with more frequent vascular embols, neural invasion and metastatic nodes. Furthermore, immunohistochemical analysis of galectin-3 showed a significant difference between mucinous and non mucinous adenocarcinoma. CONCLUSION: Based on the presented data, the epidemiological pattern and the anatomic distribution especially in the rectosigmoid region suggest diet and lifestyle to be primordial risk factors of colorectal tumorigenesis.
Asunto(s)
Adenocarcinoma Mucinoso/epidemiología , Adenocarcinoma Mucinoso/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Galectina 3/análisis , Adenocarcinoma/química , Adenocarcinoma Mucinoso/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colon Sigmoide/patología , Neoplasias Colorrectales/química , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Recto/patología , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Túnez/epidemiologíaRESUMEN
INTRODUCTION: The protein p73 is the first identified homolog of the tumor suppressor gene p53, but its function in tumor development has not been established. Indeed, the results regarding the p73 implication in colorectal cancers is still controversial. AIM: We investigated whether the p73 is implicated in colorectal cancer, whether the p73 expression is related to prognosis and whether the p73 expression is correlated with p21-ras or p53. MATERIALS AND METHODS: We performed a comparative immunohistochemical analysis of p73, p53, and p21ras proteins in primary colorectal tumor with matched normal mucosa and metastasis from 204 patients with colorectal cancer. We correlated these expressions with clinicopathologic variables and we compared the different profiles between nonmucinous carcinoma and mucinous carcinoma. RESULTS: In this study, we did not find any correlation between p73 expression, sex, age, site, differentiation and stage. Overexpression of p73 was significantly correlated with infiltrating growth pattern (P<0.0001) and nonmucinous carcinoma (P<0.0001). Furthermore, frequency and intensity of p73 expression were marquedly increased from normal mucosa (26%), to primary tumors (75%) and to metastasis (97%). Furthermore, expression of p73 was also correlated with shorter survival period. The prognostic significance of p73 expression remained, even after adjustment for the clinical and pathologic variables. The p73 expression was positively correlated only with p21ras expression (P<0.0001). CONCLUSIONS: All these findings prove that p73 expression should be considered as a valuable poor prognostic marker. Our data also suggest that TP73 gene may play a role in colorectal carcinoma development.
Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/diagnóstico , Proteínas de Unión al ADN/metabolismo , Membrana Mucosa/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adenocarcinoma Mucinoso/epidemiología , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/fisiopatología , Adenocarcinoma Mucinoso/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/fisiopatología , Neoplasias Colorrectales/secundario , Proteínas de Unión al ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Estadificación de Neoplasias , Proteínas Nucleares/genética , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Análisis de Supervivencia , Proteína Tumoral p73 , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/genéticaRESUMEN
AIM: The aim of this retrospective study was to report the results of the laparoscopic management of common bile duct stones in an unicentric series of 30 patients. METHODS: From January 2001 to April 2004. 30 patients: 23 women, 7 men (mean age: 54 years). underwent a common bile duct exploration for lithiasis through a laparoscopic approach. The patients were hospitalized for angiocholitis (n = 12), cholecystitis (n= 4), jaundice (n = 4), pancreatitis (n = 3), abnormality of hepatic tests (n = 7). All the patients underwent an intra operative cholangiography. Removal of the stones was tried in 30 cases through a choledochotomy. never through the cystic duct, using Dormia and Fogarty catheters. External biliary drainage with T tube (kehr) and postoperative cholangiography was done systematically. RESULTS: In 21 patients (70 %), removal of the stones was laparoscopically successful. The average diameter of the common bile duct was 10.5 mm (range 6-20 mm). The median number of stones was 5 (E: 1-12). The median operation time was 180mn (range 150-300mn). In 9 patients, a conversion into laparotomy was necessary for several reasons. In 2 patients with residual common bile duct, the stones were treated successfully by endoscopic sphincterotomy. There was no mortality and the morbidity rate was 10 %. The mean postoperative hospital stay was 14.7 days (range 7-18days) and 13.3 days in case of successful laparoscopic management. CONCLUSION: In 70 % of the patients, the treatment of the common bile-duct lithiasis could be achieved laparoscopically, but conventional approach and endoscopic sphincterotomy are still useful in case of failure of the laparoscopic management.