Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters

Abstract Purpose: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. Methods: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p<0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. Results: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP – 2 (p= 0.01 and – 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). Conclusions: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.

摘要 研究目的：分析结直肠腺癌中基质金属蛋白酶（matrix metalloproteinases, MMPs）1、2、9、11及16的基因与蛋白表达水平，及其与临床病理参数的相关性。方法：本研究为回顾性研究，纳入2006年至2008年间于Barretos肿瘤医院-皮奥十二世基金会（Hospital de Câncer de Barretos - Fundação Pio XII）接受手术治疗的114例结直肠腺癌患者。采用逆转录聚合酶链式反应（Reverse Transcription-Polymerase Chain Reaction, RT-PCR）检测基因表达水平，免疫组织化学（Immunohistochemistry, IHC）法检测蛋白表达水平。基因表达分析以约2倍变化（fold change, FC）且p<0.05为界，将基因分为高表达组与低表达组。免疫组织化学检测中，采用半定量分析法判定标志物阳性表达情况。组织微阵列（Tissue Microarray, TMA）标本的阅片由两名独立病理医师完成。结果：经免疫组织化学验证的基因表达结果显示，与黏液性腺癌及非特指型腺癌（adenocarcinoma NOS）的组织学类型相比，基质金属蛋白酶1（MMP-1，p=0.00，变化倍数1.57）与基质金属蛋白酶2（MMP-2，p=0.01，变化倍数-1.84）的表达具有统计学意义；与绒毛状腺癌及非特指型腺癌相比，基质金属蛋白酶9（MMP-9，p=0.01，变化倍数1.13）与基质金属蛋白酶16（MMP-16，p=0.03，变化倍数1.61）的表达具有统计学意义；基质金属蛋白酶11（MMP-11）的表达与患者男性性别特征具有统计学相关性（p=0.04，变化倍数1.65）。结论：本研究中，基质金属蛋白酶1、2、9、11及16的基因与蛋白表达水平，在至少一项被研究的临床病理参数中呈现统计学显著性差异。因此，上述基质金属蛋白酶有望成为结直肠腺癌的潜在预后评估因子。