Digestive Department, No. 3 People's Hospital/Shanghai Jiaotong University School of Medicine, 280 Mohe Road, Shanghai, China.
Dig Dis Sci. 2010 Nov;55(11):3138-46. doi: 10.1007/s10620-010-1127-3. Epub 2010 Feb 3.
The function of human macrophage metalloelastase (HME) also known as matrix metalloproteinase 12, in tumorigenesis is contradictory. The current study was designed to investigate the association of HME expression with angiogenesis and prognosis of gastric carcinomas.
In situ hybridization and immunohistochemistry were used to detect HME in human gastric carcinomas, chronic gastritis with atypical hyperplasia, and normal gastric epithelium mucosa. The results were further confirmed by RT-PCR or semi-quantitative reverse transcription polymerase chain reaction and Western blotting in gastric carcinomas and paired noncancerous tissues. VEGF and microvessel density count were also detected by immunohistochemical staining in all carcinoma tissues. The prognostic significance of HME was assessed with multiple linear regression analysis and Cox proportional hazards model.
High expression of HME protein/mRNA was observed in gastric carcinomas and atypical hyperplasia tissues compared with normal gastric epithelium mucosa, or paired noncancerous tissues. HME protein/mRNA were negatively correlated with MVD (p < 0.01), VEGF (p < 0.01), tumor differentiation grade (p < 0.05), vascular invasion (p < 0.01), and recurrence (p < 0.05-0.01). HME protein was an independent influential factor of MVD (p < 0.01). HME protein/mRNA was an independent prognostic factor of gastric carcinoma (p < 0.05-0.01). Patients with overexpression of HME protein/mRNA demonstrated a significantly better survival rate compared with those who did not (p < 0.05-0.01).
Overexpression of HME is strongly correlated with the reduced angiogenesis and vascular invasion of gastric carcinoma, and may serve as a useful predictive indicator in patients with this disease.
人巨噬细胞金属弹性蛋白酶（HME），也称为基质金属蛋白酶 12，在肿瘤发生中的作用是矛盾的。本研究旨在探讨 HME 表达与胃癌血管生成和预后的关系。
采用原位杂交和免疫组织化学方法检测人胃癌、慢性胃炎伴异型增生和正常胃黏膜上皮中 HME 的表达。在胃癌和配对非癌组织中，通过 RT-PCR 或半定量逆转录聚合酶链反应和 Western blot 进一步证实了这一结果。所有癌组织均通过免疫组织化学染色检测 VEGF 和微血管密度计数。采用多元线性回归分析和 Cox 比例风险模型评估 HME 的预后意义。
与正常胃黏膜上皮或配对非癌组织相比，胃癌和异型增生组织中 HME 蛋白/ mRNA 表达较高。HME 蛋白/ mRNA 与 MVD（p<0.01）、VEGF（p<0.01）、肿瘤分化程度（p<0.05）、血管侵犯（p<0.01）和复发（p<0.05-0.01）呈负相关。HME 蛋白是 MVD 的独立影响因素（p<0.01）。HME 蛋白/ mRNA 是胃癌的独立预后因素（p<0.05-0.01）。HME 蛋白/ mRNA 过度表达的患者生存率显著高于未表达的患者（p<0.05-0.01）。
HME 的过度表达与胃癌血管生成和血管侵犯减少密切相关，可能成为该疾病患者的有用预测指标。
