Human macrophage metalloelastase correlates with angiogenesis and prognosis of gastric carcinoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Cheng
Peng
P
Digestive Department, No. 3 People's Hospital/Shanghai Jiaotong University School of Medicine, 280 Mohe Road, Shanghai, China.
Jiang
Fo Hu
FH
Zhao
Li Min
LM
Dai
Qiang
Q
Yang
Wen Yan
WY
Zhu
Li Ming
LM
Wang
Bi Jun
BJ
Xu
Ci
C
Bao
Yu Jie
YJ
Zhang
Yan Jie
YJ
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12