组织芯片研究直肠癌中肿瘤相关基因的表达

Expressions of Tumor-associated Genes by Immuno-histochemical Staining to Tissue Microarray in Human Rectal Cancer

目的探讨人直肠癌和相应癌旁正常直肠黏膜组织中肿瘤相关基因的表达及其临床意义。方法取54例直肠癌、40例癌旁直肠黏膜组织制成54点和130点两块组织芯片,采用免疫组织化学法检测直肠组织芯片中p53、cyclin D1、bcl-2、β-catenin、c-myc、COX-2以及nm23-h1的表达。结果p53、cy-clin D1、bcl-2、β-catenin、c-myc、COX-2以及nm23-h1在直肠癌和正常直肠黏膜组织中的表达差异有统计学意义(P<0.05),其中p53与bcl-2表达之间呈正相关(r=0.332,P=0.001),β-catenin与c-myc的表达呈正相关(r=0.447,P=0.000)。在直肠癌组织中,β-catenin与年龄有关,>60岁患者中β-catenin表达率高于<60岁患者(P=0.032)。β-catenin和bcl-2虽与组织学有关,但却表现为分化程度高组织表达率高(P=0.001,P=0.006)。cyclin D1的表达与临床分期有关(P=0.039),与其他病理资料无关。nm23-h1的表达与组织分化程度、远处转移以及Duke分期有关(P=0.003,P=0.022,P=0.002),与其他临床病理资料无关。p53、c-myc、COX-2的表达与临床病理资料无关。结论p53、cyclin D1、bcl-2、β-catenin、c-myc、COX-2以及nm23-h1的异常表达与直肠癌的发生可能有关,尤其是p53、cyclin D1、bcl-2的高表达可能有助于直肠癌的早期诊断。cyclinD1的表达可能还参与了直肠癌的临床进展,nm23-h1与肿瘤的转移相关,该基因的低表达预示肿瘤的较强侵袭潜能。

Objective To study on the expressions and clinical significance of tumor-associated genes in human rectal cancers and corresponding normal para-cancer rectal mucosa. Methods 54 cases of human rectal cancer and 40 cases of para-cancer mucosa were collected and made into two tissue microarrays which containing 54 dots and 130 dots respectively. Expressions of p53, cyclinD1, bcl-2, β-catenin, c-myc, COX-2 and nm23-h1 proteins were detected by immunohistochemical staining to these tissue microarrays. Results Significant differences were found among rectal cancers and benign para-cancer mucosa according to the expressions of p53, cyclinD1, bcl-2, β-catenin, c-myc, COX-2 and nm23-h1 （P〈0.05）. Furthermore, the positive correlation of expressions of p53 with bcl-2 and β-catenin with c-myc were also found respectively in this study （r=0.332, P=0.001 and r=0.447,P=0.000）. Expression of p53, c-myc and COX-2 had no correlations of expression of p53, c-myc and COX-2 with clinicopathological data of these rectal cancer tissues. However, we found that β-catenin expression was correlated with patient years which showed proportion of β-catenin expression in patients more than 60 years old was higher than that in patients less than 60. Although β-catenin and bcl-2 expressions had relationships with historical grades, cancer tissues in this cohort with over-expression of β-catenin or bcl-2 were less facility to differentiate to advanced grade and invasive to focus and distance. Expression of cyclinD1 has no correlation with other clinicopathological parameters but clinical stages （P=0.039）. In addition to these results, the relationships of nm23-h1 expression and tissue differentiation, distance metastasis and duke’s stages were found. Conclusion Abnormal expressions of p53, cyclinD1, bcl-2, β-catenin, c-myc, COX-2 and nm23-h1, specially over-expressions of p53, cyclinD1and bcl-2 may contribute to the early diagnosis in human rectal cancer. Furthermore, aberration of cyclinD1 may involve in rectal cancer progression. Distortion of nm23-h1 may have potent role in cancer metastasis so that prognosis may increase while adjuvant therapy was used early in patients with low-expression of nm23-h1.