食管癌染色体畸变及其与临床病理参数相关性研究
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摘要
目的:食管癌是常见消化道恶性肿瘤之一,死亡率居我国十大恶性肿瘤的第四位。食管癌的早期诊断率较低,大部分患者在确诊时已到中、晚期,5年生存率大约10%;而早期食管癌患者5年生存率可达40%～70%。因此,早期发现、早期治疗是提高生存率的关键。本研究应用荧光原位杂交技术检测食管癌患者染色体畸变情况并分析其与临床病理参数之间的关系,寻找最佳的探针组合,探讨其用于食管癌辅助诊断的可行性。方法:根据文献报道和实验室前期研究结果,选取3、4、8、9、10、11、17、20号和Y染色体着丝粒探针与152例食管癌组织标本杂交,统计杂交结果并分析各染色体畸变率及其与临床指标的相关性。判定染色体畸变标准为单体和多体,对某一常染色体,一个FISH信号的细胞核大于细胞总数的20%记为单体,两个以上信号的细胞核大于细胞总数的10%记为多体;对于Y染色体(男性),多于一个信号的细胞核大于10%记为多体,没有信号的细胞大于细胞总数的20%记为缺失;缺失、单体、多体统一记为染色体畸变阳性。并且根据染色体畸变率,四探针一组随机组合,探讨探针组合用于辅助诊断食管癌的敏感性。结果:①在食管癌组织中9条染色体均显示较高的畸变率,其中144例存在至少一条染色体的异常,有6例9条染色体均有变化。②畸变率由高到低依次为8号(73%)、3号(68.4%)、20号(61.8%)、Y(55.5%)、10号(55.3%)、17号(54.6%)、11号(48.7%)、9号(48.6%)和4号(46.7%)染色体。③11、20号染色体多体与分期显著相关(p=0.011、0.005),4、9、20号染色体多体与分级显著相关(p=0.007、0.001、0.002),8、11、17、20号染色体多体与淋巴结转移显著相关(p=0.000、0.000、0.010、0.007)。④联合应用3、8、10、20号探针检测食管癌阳性率为57%,3、8、20号和Y探针组合阳性率为69%。结论:①多色荧光原位杂交可以方便、快速、半定量检测染色体畸变。②在食管鳞癌中染色体均有较高畸变率,由高到低依次为8、3、20、Y、10、17、11、9和4号染色体。③多个探针组合可用于食管鳞癌的辅助诊断,本组研究探针中,组合阳性率最高的探针分别为3、8、20、Y(男性)和3、8、10、20号染色体。
Objectives Esophageal carcinoma is one of the most common malignancies of gastrointestinal tumor, with the characteristics of high mortality. Although the prognosis of esophageal cancer has been slowly improved over the past two decades, the 5-year survival for ESCC patients who underwent operation remains as low as 7% or even less. But the early ESCC patients of 5-year survival can reach to 40% or even high. So, as early as possible to detect and cure are the key to increase the survival rate. In this investigation, we detected the chromosome aberration of ESCC and analyzed their correlation with clinicpathlogical parameters, and then look for the optimal combination of chromosomes. Methods Fluorescent labeled centromeric probes were used to assess the aberration of chromosomes 3、4、8、9、10、11、17、20 and Y. One hundred and fifty-two ESCC were analyzed by FISH. Chromosomes aberration positivity were defined as a FISH signal loss in >20% nuclei or a FISH signal in >10% nuclei. The chromosome Y positive criteria for male patients was also defined as no FISH signal in >20% nuclei or two or more signals in >10% nuclei. Results The rates of chromosomes aberration 3、4、8、9、10、11、17、20 and Y were 68.4%、46.7%、73.0%、48.6%、55.3%、48.7%、54.6%、61.8%、55.5%. The chromosomes 11 and 20 were significantly correlation with stage (p=0.011, 0.005). The chromosomes 4、9、20 were significantly correlation with grade (p=0.007、0.001、0.002). The chromosomes 8、11、17、20 were significantly correlation lymph nodes metastasis (p=0.000、0.000、0.010、0.007). Conclusions FISH was an effective method for detecting chromosomal aberrations in ESCC. There existed frequent aberrations and the mixture of centromere probes may be used for detecting ESCC. The data show that the best combination of four probes were 3、8、20 plus Y (for males) and 3、8、10 plus 20.
Objectives Esophageal carcinoma is one of the most common malignancies of gastrointestinal tumor, with the characteristics of high mortality. Although the prognosis of esophageal cancer has been slowly improved over the past two decades, the 5-year survival for ESCC patients who underwent operation remains as low as 7% or even less. But the early ESCC patients of 5-year survival can reach to 40% or even high. So, as early as possible to detect and cure are the key to increase the survival rate. In this investigation, we detected the chromosome aberration of ESCC and analyzed their correlation with clinicpathlogical parameters, and then look for the optimal combination of chromosomes. Methods Fluorescent labeled centromeric probes were used to assess the aberration of chromosomes 3、4、8、9、10、11、17、20 and Y. One hundred and fifty-two ESCC were analyzed by FISH. Chromosomes aberration positivity were defined as a FISH signal loss in >20% nuclei or a FISH signal in >10% nuclei. The chromosome Y positive criteria for male patients was also defined as no FISH signal in >20% nuclei or two or more signals in >10% nuclei. Results The rates of chromosomes aberration 3、4、8、9、10、11、17、20 and Y were 68.4%、46.7%、73.0%、48.6%、55.3%、48.7%、54.6%、61.8%、55.5%. The chromosomes 11 and 20 were significantly correlation with stage (p=0.011, 0.005). The chromosomes 4、9、20 were significantly correlation with grade (p=0.007、0.001、0.002). The chromosomes 8、11、17、20 were significantly correlation lymph nodes metastasis (p=0.000、0.000、0.010、0.007). Conclusions FISH was an effective method for detecting chromosomal aberrations in ESCC. There existed frequent aberrations and the mixture of centromere probes may be used for detecting ESCC. The data show that the best combination of four probes were 3、8、20 plus Y (for males) and 3、8、10 plus 20.
引文
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