OBJECTIVE: To investigate telomerase gene expression in precancerous mammary lesion, such as atypical ductal hyperplasia and breast cancer and to study the relationship between expression and malignant transformation....OBJECTIVE: To investigate telomerase gene expression in precancerous mammary lesion, such as atypical ductal hyperplasia and breast cancer and to study the relationship between expression and malignant transformation. METHODS: Expression of human telomerase genes (hTR) and human reverse transcriptase gene (hTRT) in 76 cases of mammary tissue was evaluated using in situ hybridization and included 50 cases of mammary hyperplasia, 6 of which were benign hyperplasia, 9 were mild atypical hyperplasia, 12 were moderate atypical hyperplasia, 23 were severe atypical hyperplasia and 26 were mammary cancer. RESULTS: The expressions of hTR and hTRT mRNA were much weaker or negative in benign hyperplasia (16.6%, 0), weak to mild moderate in atypical hyperplasia (22.2%, 11.1%, 33.3%, 25.0%), strong in severe atypical hyperplasia (60.9%, 52.1%), and significantly strong in mammary cancer (88.5%, 80.8%).The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P 0.05). CONCLUSION: Telomerase genes (hTR and hTRT) expressions are related to the transformation of atypical hyperplasia. Activated telomerase may play a role in mammary cancer development.展开更多
目的通过检测慢性胃炎、肠化生、不典型增生和胃癌组织中幽门螺杆菌(Hp)感染、蛋白激酶C(PKC)水平、细胞增殖水平以及p53突变基因表达状态探讨Hp感染在胃癌发生中的作用及其作用机制。方法采用病例对照研究,病例来源于中山医院,经内镜...目的通过检测慢性胃炎、肠化生、不典型增生和胃癌组织中幽门螺杆菌(Hp)感染、蛋白激酶C(PKC)水平、细胞增殖水平以及p53突变基因表达状态探讨Hp感染在胃癌发生中的作用及其作用机制。方法采用病例对照研究,病例来源于中山医院,经内镜和病理检查证实。Hp感染采用快速尿素酶和病理Gimsa染色检测。PKC的检测采用免疫组化EnVision^(TM)法,增殖细胞核抗原(PCNA)、突变型p53基因表达的检测采用免疫组织化学方法。结果①总的Hp感染的检出率为76.2％(138/181)。在慢性胃炎肠化生组、不典型增生组、胃癌组分别为62.0％(31/50),88.6％(39/44),78.3％(68/87),均明显高于单纯慢性胃炎对照组52.6％(20/38,P<0.05)。②PCNA增殖指数在三组病例中均处于高水平,且Hp阳性组均高于Hp阴性组。③突变型p53基因表达在肠上皮化生、不典型增生和胃癌组阳性率分别为36.0％(18/50),54.6％(24/44),57.2％(48/84)。不典型增生和胃癌组均明显高于肠上皮化生组。在肠化生组,Hp阳性病例的P53表达率明显高于Hp阴性病例(48.5％ vs15.8％,P=0.020)。但在不典型增生和胃癌组,Hp阳性与Hp阴性病例的P53突变蛋白表达率无明显差别(53.9％ vs60.0％,P=0.794;53.8％ vs 68.4％,P=0.258)。P53表达与PCNA增殖指数有明显的相关性。④PKC在慢性胃炎伴肠化生、不典型增生和胃癌组阳性表达的比例呈递增趋势,分别为16.0％,28.5％,41.8％,对照组的阳性表达率不足5％。Hp阳性组PKC表达阳性率(47/130,36.2％)高于Hp阴性组(6/41,14.6％.P=(0.010)。PKC表达组,其P53表达的阳性率和阳性表达程度均高于PKC无表达的病例,在肠化生组统计学检验差异有显著性(75.0％ vs 28.6％,P=0.012),不典型增生(66.7％ vs 50.0％,P=0.430)和胃癌(63.6％ vs 52.2％,P=0.310)统计学检验差异无显著性。结论在从慢性胃炎到肠上皮化生、不典型增生、胃癌的发生过程中,存在PKC表达水平的增高、PCNA高表达和突变型P53基因表达的异常增高,而且这种增高在肠上皮化生阶段就很明显。Hp感染在肠化生阶段促进p53基因突变,其作用途径可能系通过PKC表达增强。P53蛋白可以作为早期监测胃癌发生或高危人群(肠化生)的指标。展开更多
文摘OBJECTIVE: To investigate telomerase gene expression in precancerous mammary lesion, such as atypical ductal hyperplasia and breast cancer and to study the relationship between expression and malignant transformation. METHODS: Expression of human telomerase genes (hTR) and human reverse transcriptase gene (hTRT) in 76 cases of mammary tissue was evaluated using in situ hybridization and included 50 cases of mammary hyperplasia, 6 of which were benign hyperplasia, 9 were mild atypical hyperplasia, 12 were moderate atypical hyperplasia, 23 were severe atypical hyperplasia and 26 were mammary cancer. RESULTS: The expressions of hTR and hTRT mRNA were much weaker or negative in benign hyperplasia (16.6%, 0), weak to mild moderate in atypical hyperplasia (22.2%, 11.1%, 33.3%, 25.0%), strong in severe atypical hyperplasia (60.9%, 52.1%), and significantly strong in mammary cancer (88.5%, 80.8%).The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P 0.05). CONCLUSION: Telomerase genes (hTR and hTRT) expressions are related to the transformation of atypical hyperplasia. Activated telomerase may play a role in mammary cancer development.
文摘目的通过检测慢性胃炎、肠化生、不典型增生和胃癌组织中幽门螺杆菌(Hp)感染、蛋白激酶C(PKC)水平、细胞增殖水平以及p53突变基因表达状态探讨Hp感染在胃癌发生中的作用及其作用机制。方法采用病例对照研究,病例来源于中山医院,经内镜和病理检查证实。Hp感染采用快速尿素酶和病理Gimsa染色检测。PKC的检测采用免疫组化EnVision^(TM)法,增殖细胞核抗原(PCNA)、突变型p53基因表达的检测采用免疫组织化学方法。结果①总的Hp感染的检出率为76.2％(138/181)。在慢性胃炎肠化生组、不典型增生组、胃癌组分别为62.0％(31/50),88.6％(39/44),78.3％(68/87),均明显高于单纯慢性胃炎对照组52.6％(20/38,P<0.05)。②PCNA增殖指数在三组病例中均处于高水平,且Hp阳性组均高于Hp阴性组。③突变型p53基因表达在肠上皮化生、不典型增生和胃癌组阳性率分别为36.0％(18/50),54.6％(24/44),57.2％(48/84)。不典型增生和胃癌组均明显高于肠上皮化生组。在肠化生组,Hp阳性病例的P53表达率明显高于Hp阴性病例(48.5％ vs15.8％,P=0.020)。但在不典型增生和胃癌组,Hp阳性与Hp阴性病例的P53突变蛋白表达率无明显差别(53.9％ vs60.0％,P=0.794;53.8％ vs 68.4％,P=0.258)。P53表达与PCNA增殖指数有明显的相关性。④PKC在慢性胃炎伴肠化生、不典型增生和胃癌组阳性表达的比例呈递增趋势,分别为16.0％,28.5％,41.8％,对照组的阳性表达率不足5％。Hp阳性组PKC表达阳性率(47/130,36.2％)高于Hp阴性组(6/41,14.6％.P=(0.010)。PKC表达组,其P53表达的阳性率和阳性表达程度均高于PKC无表达的病例,在肠化生组统计学检验差异有显著性(75.0％ vs 28.6％,P=0.012),不典型增生(66.7％ vs 50.0％,P=0.430)和胃癌(63.6％ vs 52.2％,P=0.310)统计学检验差异无显著性。结论在从慢性胃炎到肠上皮化生、不典型增生、胃癌的发生过程中,存在PKC表达水平的增高、PCNA高表达和突变型P53基因表达的异常增高,而且这种增高在肠上皮化生阶段就很明显。Hp感染在肠化生阶段促进p53基因突变,其作用途径可能系通过PKC表达增强。P53蛋白可以作为早期监测胃癌发生或高危人群(肠化生)的指标。
