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碱性成纤维细胞生长因子mRNA和基质金属蛋白酶-9 mRNA表达与胃癌微血管密度、进展及预后的相关性研究

Correlative studies on bFGF mRNA and MMP-9 mRNA expressions with microvascular density, progression, and prognosis of gastric carcinomas.

作者信息

Zhao Zhong-Sheng, Zhou Ji-Lin, Yao Gen-You, Ru Guo-Qing, Ma Jie, Ruan Jun

机构信息

Department of Pathology, Zhejiang Provincial Hospital, Hangzhou 310014, Zhejiang Province, China.

出版信息

World J Gastroenterol. 2005 Jun 7;11(21):3227-33. doi: 10.3748/wjg.v11.i21.3227.

Abstract

AIM

To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.

METHODS

In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas.

RESULTS

In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09+/-11.52 and 43.75+/-13.41, respectively in piece/0.72 mm(2) in tumors with bFGFmRNA and MMP-9mRNA positive expressions, which were significantly higher than those with negative expression (29.41+/-12.47; 33.45+/-13.92 piece/0.72 mm(2), respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (r(s) = 0.211, P = 0.031; r(s) = 0.335, P = 0.001), growing pattern (r(s) = 0.324, P = 0.001; r(s) = 0.267, P = 0.006), vessel invasion (r(s) = 0.579, P = 0.001; r(s) = 0.209, P = 0.032), lymph node metastasis (r(s) = 0.405, P = 0.001; r(s) = 0.343, P = 0.001) and distant metastasis (r(s) = 0.474, P = 0.001; r(s) = 0.468, P = 0.001), but not correlated to tumor type (r(s) = 0.134, P = 0.173; r(s) = 0.103, P = 0.145) and differentiations (r(s) = 0.096, P = 0.332; r(s) = 0.102, P = 0.298). The mean MVD was much higher in the tumors with infiltrating growth at stage T(3)-T(4), with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P = 0.001) at stage T(1)-T(2) (t = 5.961, P = 0.001), with non-vessel invasion (t = 7.394, P = 0.001), non-lymph node metastasis (t = 3.819, P = 0.01) and non-distant metastasis (t = 10.578, P = 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA (t = 3.207, P = 0.002; t = 7.035, P = 0.001, respectively). The mean survival time and 5-year survival rate were lower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA.

CONCLUSION

bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bFGF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.

摘要

目的

研究碱性成纤维细胞生长因子(bFGF)和基质金属蛋白酶-9(MMP-9)在胃癌中的mRNA表达,以揭示它们与肿瘤微血管密度(MVD)、侵袭、转移及预后的关系。

方法

采用原位杂交和免疫组化技术检测105例胃癌标本中bFGFmRNA、MMP-9mRNA的表达及CD34蛋白的表达。

结果

原位杂交研究显示,bFGF mRNA和MMP-9mRNA表达的阳性率分别为60.95%和59.19%;bFGFmRNA和MMP-9mRNA阳性表达的肿瘤中,平均MVD分别为46.09±11.52和43.75±13.41个/0.72mm²,显著高于阴性表达的肿瘤(分别为29.41±12.47;33.45±13.92个/0.72mm²)。bFGFmRNA和MMP-9mRNA的阳性表达率与肿瘤浸润深度(rs = 0.211,P = 0.031;rs = 0.335,P = 0.001)、生长方式(rs = 0.324,P = 0.001;rs = 0.267,P = 0.006)、血管侵犯(rs = 0.579,P = 0.001;rs = 0.209,P = 0.032)、淋巴结转移(rs = 0.405,P = 0.001;rs = 0.343,P = 0.001)及远处转移(rs = 0.474,P = 0.001;rs = 0.468,P = 视0.001)相关,但与肿瘤类型(rs = 0.134,P = 0.173;rs = 0.103,P = 0.145)及分化程度(rs = 0.096,P = 0.332;rs = 0.102،P = 0.298)无关。T(3)-T(4)期浸润性生长、有血管侵犯、淋巴结转移及远处转移的肿瘤平均MVD明显高于T(1)-T(2)期扩展性生长类型(t = 10.105,P = 0.001)、无血管侵犯(t = 5.961,P = 0.001)、无淋巴结转移(t = 7.394,P = 0.001)及无远处转移(t = 3.819,P = 0视.01)的肿瘤。MVD与bFGFmRNA和MMP-9mRNA的表达呈正相关(t分别为3.207,P = 0.002;t = 7.035,P = 0.001)。MVD大于39.5且bFGFmRNA和MMP-9mRNA阳性表达的病例平均生存时间和5年生存率低于MVD小于于39.5且bFGFmRNA和MMP-9mRNA阴性表达的病例。

结论

bFGF和MMP-9促进胃癌血管生成。检测bFGF和MMP-9的表达可作为判断胃癌血管生成、侵袭、转移及预后的有用指标。

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