探讨大肠癌组织中细胞周期调控因子表达与微卫星不稳定性(MSI)的关系。方法　采用免疫组化、PCR-SSLP法对56例大肠癌分别进行细胞周期调控因子Cyclin d1、P16、P21WAF1/CIP1、P53、Rb以及PCNA的观测和D18S34、D17S799、D5S409、TCF-2、P53和Rb6个碱基序列位点MSI检测。结果　大肠癌MSI总阳性率44.6%，其中1个位点阳性7例，≥2个位点阳性18例，占32.1%。MSI阳性(MSI＋)大肠癌Cyclin d1、P53蛋白阳性表达率显著低于MSI阴性(MSI-)大肠癌，而P21蛋白阳性表达率显著高于MSI-肿瘤组(P＜0.05)，MSI+大肠癌P16阳性率也较MSI-组略增高，MSI+和MSI-大肠癌Rb蛋白阳性表达率较接近。结论　P21蛋白过度表达对大肠癌MSI的发生可能具有较重要的促进作用，Cyclin d1、P53蛋白表达减少或P16蛋白过度表达与大肠癌MSI的发生可能也有关。

Relationship between the expression of cell cycle regulators and microsatellite instability in colorectal carcinomas

YAN Xiaochu, LIU Fengxuan. FANG dianchun, et al.

　　（Department of Pathology, Southwest Hospital, The Third Military Medical university, Chongqing 400038, China）

　　【Abstract】　Objective　To explore the relationship between the expression of cell cycle regulators and microsatellite instability (MSI) in colorectal carcinomas(CRC).Methods　The expression of cell cycle regulators cyclin D1, P16, P21WAF1/CIP1, p53, Rb and PCNA were detected by immunohistochemical staining, and MSI at six microsatellite loci (D18S34, D17S799, D5S409, TCF-2, Rb and P53) were examined by PCR-SSLP in 56 cases of colorectal carcinomas.Results　The overall positive rate of MSI of CRC was 44.6% (25/56). MSI was positive at 1 locus in 7 cases, at 2 and more than 2 loci in 18 cases. In CRC with MSI, the positive rate of cyclin D1 and P53 protein was significantly lower, while that of P21 protein was significantly higher than those without MSI (P＜0.05). The positive rate of P16 in CRC with MSI was higher than those without MSI. The expression of Rb proteins was similar in frequency in CRC with or without MSI.Conclusion　Overexpression of P21 may play an important role in MSI genesis in CRC. It may also be related to decreased expression of cyclin D1 and P53 and overexpression of P16.

　　【Subject words】　Colorectal neoplasms;　Cell cycle;　Microsatellite instability

　　大肠癌发生机制较为复杂，涉及一系列分子遗传学的改变。最近国外研究发现遗传性非息肉病性大肠癌(hereditary non-polyposis colorectal cancer，HNPCC)和部分散发性大肠癌的发生是由于微卫星不稳定(microsatellite instability,MSI)所致［1］。而细胞周期调控的分子机制正成为肿瘤发生发展研究的热点［2］。细胞周期调控因子表达与大肠癌MSI的关系仍不十分清楚。为此，我们采用免疫组化、PCR-SSLP法对56例大肠癌进行细胞周期调控因子表达和MSI检测，探讨细胞周期调控因子在大肠癌MSI发生中的作用和意义。

　　材料与方法

　　1.标本：采用我院1987～1996年间手术切除的56例大肠癌标本，其中新鲜组织22例，石蜡组织34例。每例同时采集残端正常粘膜组织。

[1] [2] [3] [4] 下一页