采用原位杂交技术检测正常大肠粘膜、息肉及癌组织中P16、细胞周期素D1、（Cyclin　D1）的表达情况，并结合临床资料进行分析。结果显示，P16在正常大肠粘膜中的阳性表达率最高，息肉组织次之，癌组织最低；癌组织与正常大肠粘膜和息肉组织比较差异显著（P＜0.005）。对大肠癌患者术后随访2年发现，其死亡与存活者的P16和Cyclin　D1亦有明显差异（P＜0.01）。正常大肠粘膜和炎性息肉组织未发现Cyclin　D1过度表达，腺瘤样息肉表达率为7.7％，癌组织表达率大于65％，与正常大肠粘膜和息肉组织比较差异显著（P＜0.005）。相关性分析显示，P16、Cyclin　D1在大肠粘膜组织中多数呈反向表达。提示P16、Cyclin　D1在大肠癌发生过程中起重要的作用，其反向表达趋势说明可能存在相互抑制机制。

　　Abstract The P16 and cyclin D1 expressions was determined in the normal colorectal mucosa，polypous tissue and colorectal carcinoma by using hybridization in situ.the results showed that the positive staining of P16 was the highest in normal colorectal tissue，polypus was the second and colorectal cancer was the lowest.There was a significant difference between normal colorectal tissue and cancer group（P＜0.05），and showed same result in survival group and death group by follow-up survey 2 years（P＜0.01）.The positive for Cyclin D1 was not showed in normal colorectal tissue and inflammatory polypous tissue.The positive staining rate was higher 65％ in colorectal cancer（P＜0.005）.An interesting observation was that inverse expression between P16 and Cyclin D1 was showed in most of the colorectal cancer.P16 and Cyclin D1 was closely related to the occurrence and development of colorectal cancer.The inverse expression between P16 and CYclin D1 was closely related to the occurrence and development of colorectal cancer.The inverse expression between P16 and Cyclin D1 suggests antagonism between the two，and it plays an important role in the estimation of prognosis.

　　Key Words Colorectal cancer P16 Cyclin D1 hybridization in situ

　　人体实体肿瘤的发生和发展是一个十分复杂的过程。现已确定肿瘤由基因病变引起，其中癌基因活化（基因扩增和过度表达等）、抑癌基因失活（突变等）及其他细胞周期调节因子调控失常与肿瘤的发生、发展有密切关系。为了探讨多肿瘤抑制基因P16和Cyclin　D1在大肠粘膜上皮细胞的表达情况，我们采用原位杂交技术对84例大肠癌、94例结肠息肉患者的病变进行了P16、Cyclin　D1测定，现报告如下。

　　1　资料与方法

　　本文大肠癌患者84例（结肠癌46例、直肠癌38例），结肠息肉94例，无大肠疾病者86例。将手术切除的癌组织、结肠镜下取出的息肉组织及正常大肠粘膜组织迅速用中性福尔马林固定，常规组织脱水后，用石蜡包埋并连续切片，分别进行HE染色，作组织病理学检查和DNA原位杂交实验。根据细胞形态和组织结构变化，本文大肠上皮正常86例；高、中分化腺癌31例，低分化腺癌25例，粘液腺癌16例，未分化癌12例；炎性息肉42例，腺瘤样息肉52例。

　　DNA原位杂交实验试剂分别由美国Cold　Spring　Harbor实验室和Scripps实验室惠赠，实验过程按说明严格操作。各组织样本除用反义RNA探针进行杂交外，同时用不加探针作为对照；最后镜下观察比较显色结果。统计学处理方法采用两样本率比较的X2检验，P＜0.05为显著性差异。

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