Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis
Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis
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DOI：
10.1007/s00384-006-0093-x
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发表时间：
2007-02-01
影响因子：
2.8
通讯作者：
Sarli, Leopoldo
中科院分区：
文献类型：
--
作者：
Azzoni, Cinzia;Bottarelli, Lorena;Sarli, Leopoldo
背景和目的：结直肠癌(CRC)是全球第四大最常见的癌症。发生在脾弯曲近端或远端的癌在流行病学发病率、形态和分子改变方面存在差异，这表明根据起源部位存在两种类型的癌。方法：分析散发性结直肠癌患者的临床病理特征、微卫星不稳定性、18q、8p和4p染色体杂合性缺失(LOH)，以及hM1h1、hMsh2、FHit、p27和COX-2免疫组织化学染色。结果：散发性结直肠癌近端粘液组织类型多于远端(p<；0.004)。MSI表型在近端肿瘤中的表达频率高于远端肿瘤(p<；0.001)，而且免疫组织化学hMLH1、FHIT、p27的表达降低或缺失在近端肿瘤中的发生率高于远端肿瘤(p<；0.001和0.01)。相反，远端肿瘤18q基因杂合性缺失频率高于近端肿瘤(p=0.002)。近端和远端肿瘤的8P杂合性缺失频率和hMsh2和P53蛋白的表达差异无统计学意义。结论：这些不同的特征可能反映了不同的致癌遗传途径，支持了近端和远端肿瘤发生机制不同的假说，对治疗具有潜在的指导意义。
Background and aims: Colorectal cancer (CRC) ranks as the fourth most frequently diagnosed cancer worldwide. CRCs that arise proximally or distally to the splenic flexure show differences in epidemiologic incidence, morphology, and molecular alterations, suggesting the existence of two categories of CRC based on the site of origin. The aim of the present work is to investigate the histological and molecular differences between CRCs located proximally and distally to the splenic flexure, and their potential involvement in tumor prognosis and therapeutic strategies.Methods: We evaluated 120 patients affected by sporadic CRC for clinicopathologic features, microsatellite instability (MSI), loss of heterozygosity (LOH) of chromosomes 18q, 8p, and 4p; they were also investigated for hMlh1, hMsh2, Fhit, p27, and Cox-2 immunostaining.Results: The mucinous histotype was more frequent in the proximal than in the distal CRCs (p < 0.004). The frequency of MSI phenotype was higher in proximal than in distal tumors (p < 0.001); moreover, reduced or absent hMlh1, Fhit, p27 immunohistochemical expressions were more frequent in proximal than in distal tumors (p < 0.001 and 0.01 for p27). In contrast, the frequency of LOH in 18q was higher in distal than in proximal tumors (p=0.002). No significant differences were observed between proximal and distal tumors in the frequency of LOH in 8p and altered expression of hMsh2 and p53 protein.Conclusion: These different features may reflect different genetic pathways of carcinogenesis and support the hypothesis of a different mechanism of cancer development between the proximal and the distal colon, with potential implications in the therapeutic approach.