结直肠癌微卫星不稳定(MSI)与其发病及预后的关系

Relationship of Microsatellite Instability with the Incidence and Prognosis of Colorectal Cancer

抑癌基因及癌基因之间的相互作用是结直肠癌发病主要发病原因,近年研究发现微卫星不稳定成为结直肠癌发病另一重要机制,尤其是遗传性非息肉病性结直肠癌(hereditary non-polyposis colorectal cancer,HNPCC)及部分散发性结直肠癌发生的重要原因。微卫星不稳定的结直肠患者具有独特的临床病理特征,如低分化、黏液腺癌、多位于右半结肠、淋巴细胞浸润明显等。化疗是结直肠癌患者手术后重要治疗手段,氟尿嘧啶类药物为结直肠癌患者化疗的基本药物,因此结直肠癌患者对于氟尿嘧啶类药物敏感性成为患者能否从化疗中获益的重要因素,也成为各位学者的研究热点。近年来有学者提出微卫星不稳定及其他分子标记物可预测结直肠癌患者化疗敏感性,同时也可成为判断预后的指标。微卫星不稳定将来可成为结直肠癌患者的预后及化疗敏感性的判断因素,也可为个体化治疗提供理论依据,但目前尚需大样本的前瞻性临床试验进一步证实。结直肠癌目前在国内外发病率均逐渐升高,成为危害人类生命的重要疾病,且遗传倾向明显,是目前人类恶性肿瘤中遗传变化最明显的肿瘤。对于结直肠癌的发病研究表明,染色体不稳定(chromosomeinstability)为结直肠癌发病的主要原因,其机制仍未完全阐明。近年的研究发现微卫星不稳定(microsatelite instability)为结直肠癌发病的另一重要机制,是遗传性非息肉病性结直肠癌(hereditarynon-polyposis colorectal cancer,HNPCC)及部分散发性结直肠癌发生的重要原因。目前关于微卫星不稳定的研究不仅于发病机制上,与结直肠癌预后的关系也成为目前研究的热点。

In the past, antioncogene-oncogene interaction was considered as a major mechanism in colorectal cancer development. However, recently, microsatellite instability was found to be another important mechanism in colorectal cancer, especially hereditary non-polyposis colorectal cancer. These patients usually have unique clinicopathologic features, such as poorly differentiated adenocarcinoma on the right side, mucinous colon cancers, and abundance of tumor-infiltrating lymphocytes. Chemotherapy is a major post- operative therapeutic method, and fluorouracil-based chemotherapy is the foundation of chemotherapy in colorectal cancer patients. Thus, the sensibility of the fluorouracil plays an important role in the treatment of colorectal cancer patients and has become a popular research topic. Recently, some scholars have suggested that microsatellite instability and other biological molecular markers can predict the sensibility of chemotherapy and the prognosis of colorectal cancer patients. Thus, microsatellite instability may be a good prognostic factor and indicator of chemotherapy response. It can also be a theoretical evidence for individual treatment of cancer. However, clinical trials with larger tissue samples are needed to confirm the above findings.