Sillanpää S, Anttila M, Voutilainen K, Ropponen K, Turpeenniemi-Hujanen T, Puistola U, Tammi R, Tammi M, Sironen R, Saarikoski S, Kosma V-M
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio, and Department of Clinical Pathology, Kuopio University Hospital, Finland.
Gynecol Oncol. 2007 Feb;104(2):296-303. doi: 10.1016/j.ygyno.2006.09.004. Epub 2006 Oct 10.
We investigated the expression of matrix metalloproteinase-9 (MMP-9) and its relation to clinicopathologic factors and survival and also to previously analyzed expressions of CD44 and hyaluronan in epithelial ovarian cancer.
The expression of MMP-9 was analyzed immunohistochemically in 292 primary tumors and their 31 metastases.
A low proportion of strong MMP-9 expression in cancer cells and high stromal MMP-9 expression correlated with advanced stage of the tumor (p=0.003, p=0.02, respectively). Stromal MMP-9 expression significantly correlated with hyaluronan positivity (p<0.0005), whereas MMP-9 did not correlate with CD44. In univariate analysis, a longer 10-year disease-related survival (DRS) was found in patients with a high proportion of MMP-9 or strong MMP-9 expression in cancer cells (p=0.02, p=0.05, respectively). However, high stromal expression of MMP-9 indicated short DRS (p=0.01). In multivariate analysis of all patients, MMP-9 expressing cancer or stromal cells were not independent prognostic factors, while in FIGO stage I patients a high percentage of MMP-9 positive cancer cells was associated with long DRS (p=0.008).
These data suggest that MMP-9 has a dual role in tumor progression, acting against tumor advancement when in tumor epithelium and promoting tumor progression while in the stroma.
我们研究了基质金属蛋白酶-9（MMP-9）的表达及其与临床病理因素、生存率的关系，以及其与先前分析的上皮性卵巢癌中CD44和透明质酸表达的关系。
采用免疫组织化学方法分析292例原发性肿瘤及其31处转移灶中MMP-9的表达。
癌细胞中MMP-9强表达比例低和基质中MMP-9高表达与肿瘤晚期相关（分别为p = 0.003，p = 0.02）。基质中MMP-9表达与透明质酸阳性显著相关（p < 0.0005），而MMP-9与CD44不相关。单因素分析显示，癌细胞中MMP-9比例高或MMP-9强表达的患者10年疾病相关生存率（DRS）较长（分别为p = 0.02，p = 0.05）。然而，基质中MMP-9高表达提示DRS短（p = 0.01）。在所有患者的多因素分析中，表达MMP-9的癌细胞或基质细胞不是独立的预后因素，而在国际妇产科联盟（FIGO）I期患者中，MMP-9阳性癌细胞比例高与DRS长相关（p = 0.008）。
这些数据表明，MMP-9在肿瘤进展中具有双重作用，在肿瘤上皮中时对抗肿瘤进展，而在基质中时促进肿瘤进展。
