Mönig S P, Baldus S E, Hennecken J K, Spiecker D B, Grass G, Schneider P M, Thiele J, Dienes H P, Hölscher A H
Department of Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany.
Histopathology. 2001 Dec;39(6):597-602. doi: 10.1046/j.1365-2559.2001.01306.x.
One important step in tumour invasion is the penetration of the basement membrane. Matrix metalloproteinases (MMPs) play a key role in the migration of normal and malignant cells through the basement membrane. The aim of this study was to investigate correlations between matrix metalloproteinase 2 (MMP-2) immunoreactivity and currently used classification systems and possible relationships between lymph node metastasis and MMP-2 expression.
This prospective study analysed specimens obtained from 114 gastric cancer patients (mean age 64 years; range 33-86 years) who underwent gastrectomy with extended lymphadenectomy. All specimens were categorized according to UICC classification, WHO classification, tumour differentiation, Laurén classification, Ming classification and Goseki classification. Formalin-fixed paraffin-embedded tumour specimens were stained using an avidin-biotin complex peroxidase assay. MMP-2 expression in the tumour epithelium was studied by immunohistochemistry with semiquantitative (score 0-3) evaluation. The MMP-2 staining pattern was positive (score 1-3) in 93 (81.6%) specimens and negative (score 0) in 21 (18.4%) samples. No significant correlations were found between MMP-2 expression and other variables such as age, tumour differentiation, WHO, Lauren, Goseki, and Ming classifications. In contrast, the intensity of MMP-2 staining in tumour cells correlated significantly with depth of tumour infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), and UICC stage.
Expression of MMP-2 is strongly associated with tumour progression and lymph node metastasis in gastric cancer. Therefore MMP-2 staining may be clinically useful as predictor of tumour progression, especially for lymph node metastasis.
肿瘤侵袭的一个重要步骤是基底膜的穿透。基质金属蛋白酶（MMPs）在正常细胞和恶性细胞通过基底膜的迁移中起关键作用。本研究的目的是探讨基质金属蛋白酶2（MMP-2）免疫反应性与目前使用的分类系统之间的相关性，以及淋巴结转移与MMP-2表达之间的可能关系。
这项前瞻性研究分析了114例接受胃癌根治术及扩大淋巴结清扫术的胃癌患者（平均年龄64岁；范围33 - 86岁）的标本。所有标本根据国际抗癌联盟（UICC）分类、世界卫生组织（WHO）分类、肿瘤分化程度、劳伦（Laurén）分类、明（Ming）分类和五木（Goseki）分类进行分类。采用抗生物素蛋白-生物素复合物过氧化物酶法对福尔马林固定石蜡包埋的肿瘤标本进行染色。通过免疫组织化学和半定量（评分0 - 3）评估研究肿瘤上皮中MMP-2的表达。MMP-2染色模式在93例（81.6%）标本中呈阳性（评分1 - 3），在21例（18.4%）标本中呈阴性（评分0）。未发现MMP-2表达与年龄、肿瘤分化程度、WHO、劳伦、五木和明分类等其他变量之间存在显著相关性。相比之下，肿瘤细胞中MMP-2染色强度与肿瘤浸润深度（T分期）、淋巴结转移（N分期）、远处转移（M分期）和UICC分期显著相关。
MMP-2的表达与胃癌的肿瘤进展和淋巴结转移密切相关。因此，MMP-2染色在临床上可能有助于预测肿瘤进展，尤其是淋巴结转移。
