Lleonart M E, García-Foncillas J, Sánchez-Prieto R, Martín P, Moreno A, Salas C, Ramón y Cajal S
Department of Pathology, Clínica Puerta de Hierro, Madrid, Spain.
Cancer. 1998 Sep 1;83(5):889-95.
Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis.
One hundred and twenty-five cases of sporadic colon carcinoma (50 in the right colon and 75 in the left colon in patients with no family history of colon carcinoma) were studied. Status of the p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing at exons 5-8. Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing.
In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No correlation between microsatellite instability and p53 mutations was detected. In the left colon carcinoma cases, p53 mutations were detected in 41% of tumors and microsatellite instability in 14%; neither finding was related to the tumor size. Mutations of the hMLH1 and hMSH2 mismatch repair genes were detected in 7 of 24 cases with marked microsatellite instability.
Microsatellite instability is prone to occur in sporadic right colon carcinoma during tumor growth and is not associated significantly with mutations in the hMLH1 and hMSH2 mismatch repair genes or in the p53 gene. Concomitant detection of microsatellite instability and p53 mutations in right colon carcinoma is associated with the presence of lymph node metastases.
左半结肠癌和右半结肠癌可表现出不同的临床、病理及遗传学特征。本研究旨在明确散发性结肠癌的多种分子遗传学改变，并将其与肿瘤位置及淋巴结转移相关联。
对125例散发性结肠癌病例（其中50例位于右半结肠，75例位于左半结肠，患者均无结肠癌家族史）进行研究。通过聚合酶链反应（PCR）、单链构象多态性分析及对第5 - 8外显子进行测序来评估p53基因状态。利用位于18号染色体上的5个微卫星标记分析微卫星不稳定性。通过PCR和测序对发现具有微卫星不稳定性的肿瘤研究错配修复基因hMLH1和hMSH2。
在研究的125例病例中，有53例肿瘤存在p53基因突变。p53基因突变与右半结肠癌病例的淋巴结转移相关（61%），且所有存在p53基因突变及微卫星不稳定性的病例均为美国癌症联合委员会/国际抗癌联盟（AJCC/UICC）Ⅲ期（杜克分期C期）。在右半结肠癌病例中，微卫星不稳定性发生率与肿瘤大小相关（直径< 4 cm的肿瘤为19%，直径> 4 cm的肿瘤为34%）。未检测到微卫星不稳定性与p53基因突变之间存在相关性。在左半结肠癌病例中，41%的肿瘤检测到p53基因突变，14%检测到微卫星不稳定性；两者均与肿瘤大小无关。在24例具有明显微卫星不稳定性的病例中，有7例检测到hMLH1和hMSH2错配修复基因突变。
微卫星不稳定性在散发性右半结肠癌肿瘤生长过程中易于发生，且与hMLH1和hMSH2错配修复基因或p53基因的突变无显著关联。右半结肠癌中微卫星不稳定性和p53基因突变的同时检测与淋巴结转移的存在相关。
