Jeffery Natalie, McLean Mairi H, El-Omar Emad M, Murray Graeme I
Department of Pathology, University of Aberdeen, Aberdeen, UK.
Histopathology. 2009 Jun;54(7):820-8. doi: 10.1111/j.1365-2559.2009.03301.x.
The matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) system has a major role in tumour invasion and metastasis. Roles in pathways involved in early tumour development are also being identified for this system, and the aim of this study was to define the expression profile of the major MMPs and TIMPs in colorectal polyp cancers.
The expression and cellular localization of individual MMPs and TIMPs was determined in colorectal polyp cancers by immunohistochemistry. All the MMPs and TIMPs showed immunoreactivity in carcinomatous epithelium. MMP1 (P < 0.001), MMP2 (P = 0.003), MMP3 (P = 0.004), TIMP1 (P = 0.01) and TIMP2 (P < 0.001) showed significant increases in immunoreactivity in carcinomatous epithelium compared with adenomatous epithelium. MMP7 showed immunoreactivity in carcinomatous epithelium, but showed no immunoreactivity in either normal epithelium or adenomatous epithelium. MMP and TIMP expression was limited in normal epithelium to MMP1, MMP2 and TIMP3.
This study defines the expression profile of MMPs and TIMPs in colorectal polyp cancers and shows that the increased expression of MMPs and TIMPs occurs at an early stage of colorectal neoplasia. It provides evidence to support the hypothesis that these molecules have a key involvement in the early stages of tumour development.
基质金属蛋白酶（MMP）/金属蛋白酶组织抑制剂（TIMP）系统在肿瘤侵袭和转移中起主要作用。该系统在肿瘤早期发展相关通路中的作用也正在被明确，本研究的目的是确定结直肠息肉癌中主要MMP和TIMP的表达谱。
通过免疫组织化学法测定结直肠息肉癌中各MMP和TIMP的表达及细胞定位。所有MMP和TIMP在癌上皮中均显示免疫反应性。与腺瘤上皮相比，MMP1（P < 0.001）、MMP2（P = 0.003）、MMP3（P = 0.004）、TIMP1（P = 0.01）和TIMP2（P < 0.001）在癌上皮中的免疫反应性显著增加。MMP7在癌上皮中显示免疫反应性，但在正常上皮或腺瘤上皮中均未显示免疫反应性。正常上皮中MMP和TIMP的表达仅限于MMP1、MMP2和TIMP3。
本研究确定了结直肠息肉癌中MMP和TIMP的表达谱，并表明MMP和TIMP的表达增加发生在结直肠癌变的早期阶段。它为支持这些分子在肿瘤发展早期起关键作用这一假说提供了证据。
