ABSTRACT
Abstract Background In the current study we aimed to find out the impact of cytokine-inducible Src homology 2 domain protein (CISH) gene polymorphisms on the risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Materials and methods Polymorphisms of CISH rs2239751, rs414171, and rs6768300 were determined in 200 PTB patients and 200 healthy subjects using T-ARMS-PCR or PCR-RFLP method. Results The results showed that rs414171 A>T genotypes significantly decreased the risk of PTB (OR = 0.16, 95% CI = 0.10–0.27, p < 0.0001, AT vs AA; OR = 0.31, 95% CI = 0.14–0.68, p < 0.0001, TT vs AA; OR = 0.19, 95% CI = 0.12–0.29, p < 0.0001, AT+TT vs AA; OR = 0.29, 95%CI = 0.20–0.42, p < 0.0001, T vs A). For rs6768300, the findings indicated that this variant decreased the risk of PTB (OR = 0.52, 95% CI = 0.33–0.82, p = 0.005, CG vs GG; OR = 0.57, 95% CI = 0.38–0.87, p = 0.012, C vs G). No significant association was observed between CISH rs2239751 polymorphism and risk/protection of PTB. Conclusion Our findings indicated that CISH rs414171 and rs6768300 variants might be associated with protection from PTB.
Subject(s)
Humans , Male , Female , Middle Aged , Tuberculosis, Pulmonary/genetics , Genetic Predisposition to Disease/genetics , Suppressor of Cytokine Signaling Proteins/genetics , Case-Control Studies , Reverse Transcriptase Polymerase Chain Reaction , Gene Frequency , Genotype , IranABSTRACT
BACKGROUND: In the current study we aimed to find out the impact of cytokine-inducible Src homology 2 domain protein (CISH) gene polymorphisms on the risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. MATERIALS AND METHODS: Polymorphisms of CISH rs2239751, rs414171, and rs6768300 were determined in 200 PTB patients and 200 healthy subjects using T-ARMS-PCR or PCR-RFLP method. RESULTS: The results showed that rs414171 A>T genotypes significantly decreased the risk of PTB (OR=0.16, 95% CI=0.10-0.27, p<0.0001, AT vs AA; OR=0.31, 95% CI=0.14-0.68, p<0.0001, TT vs AA; OR=0.19, 95% CI=0.12-0.29, p<0.0001, AT+TT vs AA; OR=0.29, 95%CI=0.20-0.42, p<0.0001, T vs A). For rs6768300, the findings indicated that this variant decreased the risk of PTB (OR=0.52, 95% CI=0.33-0.82, p=0.005, CG vs GG; OR=0.57, 95% CI=0.38-0.87, p=0.012, C vs G). No significant association was observed between CISH rs2239751 polymorphism and risk/protection of PTB. CONCLUSION: Our findings indicated that CISH rs414171 and rs6768300 variants might be associated with protection from PTB.
Subject(s)
Genetic Predisposition to Disease/genetics , Suppressor of Cytokine Signaling Proteins/genetics , Tuberculosis, Pulmonary/genetics , Case-Control Studies , Female , Gene Frequency , Genotype , Humans , Iran , Male , Middle Aged , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
El protooncogén HER2 se encuentra localizado en el cromosoma 17. Codifica una glicoproteína transmembrana llamada receptor del factor de crecimiento epidérmico humano 2 (HER2). Está amplificado a bajos niveles en muchos tejidos normales y regula el crecimiento, diferenciación y muerte celular. La sobreexpresión de HER2 es el resultado de anormalidades en la amplificación del oncogén HER2. El objetivo de este trabajo fue evaluar la amplificación del oncogén HER2 en pacientes con cáncer de mama a través de la técnica de hibridación in situ cromogénica (CISH). La muestra estuvo constituida por 200 biopsias fijadas en formol al 10%, procesadas por las técnicas habituales hasta la inclusión en parafina, correspondientes a pacientes diagnosticadas con carcinoma ductal infiltrante de la mama, procedentes de consulta privada y del Instituto de Oncología "Dr. Miguel Pérez Carreño", con estudio inmunohistoquímico realizado en el Hospital Metropolitano del Norte en Valencia. Se encontró una asociación estadísticamente significativa (p<0,001) de la amplificación de HER2 con los diferentes niveles cuantitativos del producto de expresión del gen. Cabe destacar que hubo 16 (11%) de 146 casos considerados negativos desde el punto de vista inmunohistoquímico para la expresión de HER2, que resultaron amplificados para el oncogén a través de la CISH. Asimismo, más de la mitad (52,4%) de los casos positivos (3+) no presentaron amplificación. Este estudio demuestra la importancia de realizar la determinación de la amplificación de HER2 en los casos con resultado de 1+ por inmunohistoquímica, al evidenciar que el 12,3% de los casos son positivos a la amplificación del oncogén.
HER2 proto-oncogene is located on chromosome 17. It encodes a transmembrane glycoprotein called human epidermal growth factor receptor 2 (HER2). It is amplified at low levels in many normal tissues and regulates growth, differentiation and cell death. HER2 overexpression is the result of abnormalities in the HER2 oncogene amplification. The aim of this study was to evaluate the HER2 oncogene amplification in patients with breast cancer through the chromogenic in situ hybridization (CISH) technique. The sample consisted of 200 biopsies fixed in 10% formalin, processed by standard techniques to paraffin embedding, from patients diagnosed with infiltrating ductal carcinoma of the breast, coming from private practice and the Institute of Oncology "Dr. Miguel Pérez Carreño", with immunohistochemical study performed at Northern Metropolitan Hospital in Valencia. It was found a statistically significant association (p<0.001) of HER2 amplification with different quantitative levels of the product of the gene expression. It is noteworthy that there were 16 (11%) of 146 cases considered negative from the immunohistochemical point of view for the HER2 expression, that proved to be amplified for the oncogene through the CISH. Likewise, it is emphasized that more than half (52.4%) of the positive cases (3+) showed no amplification. This study shows the importance of the determination of HER2 amplification in cases result of 1+ by immunohistochemistry, demonstrating a 12.3% positive for these cases to the oncogene amplification.
ABSTRACT
Human epidermal growth factor receptor 2 (HER2) has been evaluated in breast cancer patients to identify those most likely to benefit from herceptin-targeted therapy. HER2 amplification, detected in 20-30% of invasive breast tumors, is associated with reduced survival and metastasis. The most frequently used technique for evaluating HER2 protein status as a routine procedure is immunohistochemistry (IHC). HER2 copy number alterations have also been evaluated by fluorescence in situ hybridization (FISH) in moderate immunoexpression (IHC 2+) cases. An alternative procedure to evaluate gene amplification is chromogenic in situ hybridization (CISH), which has some advantages over FISH, including the correlation between HER2 status and morphological features. Other methodologies have also been used, such as silver-enhanced in situ hybridization (SISH) and quantitative real-time RT-PCR, to determine the number of HER2 gene copies and expression, respectively. Here we will present a short and comprehensive review of the current advances concerning HER2 evaluation in human breast cancer.