RESUMO
Background: Determining the risk of malignant behaviour and mutational status of gastrointestinal stromal tumours (GISTs) guide the management decision and allow optimal individualized patient treatment. Objectives: To determine clinicopathological, immunohistochemical (IHC), risk and KIT mutational findings of GISTs in Sudanese patients. Methods: Histological slides were reviewed, IHC for DOG-1 and CD117 performed and hotspot KIT mutations examined. The risk group was assigned using combined risk criteria. Results: 21 of the 36 patients (58.3%) were males (mean age, 54.83 ±12.57; range, 26-71). Abdominal pain and mass were the most frequent symptoms. Mean tumor size (±SD) was 11.6(±5.82) cm. Either CD117, DOG1 or both were positive in all cases. Using risk criteria, 33.3% (n=12) were clinically malignant at presentation, 13.9% (n=5) high risk, 16.7% (n=6) intermediate, 27.8% (n=10) low risk and 2.8% (n=1) very low risk. Sixteen of 23 (70%) tested cases had KIT (14 exon 11 and two exon 9) mutations. Six tumors were wild type. Exon 11 deletions (p.I563-L576 del and p.V559-N566delinsD) significantly correlate with disease recurrence (p-value: 0.028). Conclusions: Sudanese patients with GIST tend to present late. Nearly half of them correspond to the malignant/high-risk category. The frequency of KIT mutations (79.31%) is in line with the literature.
Assuntos
Tumores do Estroma Gastrointestinal , Masculino , Feminino , Humanos , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Recidiva Local de Neoplasia , Mutação , ÉxonsAssuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Imuno-Histoquímica/métodos , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Análise Serial de Tecidos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Reprodutibilidade dos Testes , SudãoRESUMO
OBJECTIVE: African populations, including the Sudanese, are underrepresented in warfarin pharmacogenetic studies. We designed a study to determine the associations between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in Sudanese patients, one of the most genetically diverse populations in Africa. MATERIAL AND METHODS: The effect of the CYP2C9 polymorphisms (*2, *3, *5, *6, *8, *9, and *11), 20 VKORC1 tag SNPs and haplotypes, and clinical covariates were comprehensively assessed in 203 Sudanese warfarin-treated patients. RESULTS: Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8 mg/day, P < 0.001). SNPs around the VKORC1 and POL3S genes were divided into two haplotype blocks in Sudanese populations. According to multiple linear regression results, rs8050984, rs7294, and rs7199949 in the VKORC1 and POL3S genes (P <0.001, <0.001, <0.001, respectively), CYP2C9 genotype (*2, *5, *6, *11; P < 0.001), body weight (P = 0.04), target INR (P = 0.007), and concurrent medications (P = 0.029) could explain about 36.7% of the total warfarin dose variation. CONCLUSION: Our data revealed that VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients. Our data suggest that combinations of the SNPs may improve predictions of warfarin dose requirements.
Assuntos
Anticoagulantes/administração & dosagem , Hidrocarboneto de Aril Hidroxilases/genética , Haplótipos , Oxigenases de Função Mista/genética , Polimorfismo de Nucleotídeo Único , Varfarina/administração & dosagem , Adolescente , Adulto , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , População Negra/genética , Citocromo P-450 CYP2C9 , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sudão , Vitamina K Epóxido Redutases , Varfarina/efeitos adversos , Varfarina/uso terapêutico , Adulto JovemRESUMO
Basal-like breast cancer, an aggressive subtype associated with high grade, poor prognosis, and younger age, is reported frequently in Africa. We analyzed the expression of the basal cytokeratins (CKs) 5/6 and 17 in a case series from Central Sudan and investigated correlations among basal CK status, ER, PgR, and Her-2/neu, and individual/clinicopathological data. Of 113 primary breast cancers 26 (23%), 38 (34%), and 46 (41%) were, respectively, positive for CK5/6, CK17, and combined basal CKs (CK5/6 and/or CK17). Combined basal CK+ status was associated with higher grade (P < .03) and inversely correlated with ER (P < .002), PgR (P = .004) and combined ER and/or PgR (P < .0002). Two clusters based on all tested markers were generated by hierarchical cluster analysis and k-mean clustering: I: designated "hormone receptors positive/luminal-like" and II: designated "hormone receptors negative", including both basal-like and Her-2/neu+ tumors. The most important factors for dataset variance were ER status, followed by PgR, CK17, and CK5/6 statuses. Overall basal CKs were expressed in a fraction of cases comparable to that reported for East and West African case series. Lack of associations with age and tumor size may represent a special feature of basal-like breast cancer in Sudan.
