Fundyler Olga, Khanna Manish, Smoller Bruce R
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Mod Pathol. 2004 May;17(5):496-502. doi: 10.1038/modpathol.3800066.
Matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix. Tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites. Gelatinases, particularly gelatinase A (matrix metalloproteinase-2), demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions. Matrix metalloproteinase-2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types, including squamous cell carcinoma arising on mucous membranes. However, correlation between matrix metalloproteinase-2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present. In this study, we used immunohistochemical techniques to examine the expression of matrix metalloproteinase-2 in 10 actinic keratosis, 15 in situ, 13 invasive, 13 primary (with documented metastatic disease), 11 metastatic, and 8 recurrent squamous cell carcinoma cases. We found that while the average staining intensity (scale 0-3+, 3+ being strongest) of actinic keratosis and in situ lesions was not statistically significant (0.87-1.3 and 0.75-1.4, respectively), the average staining intensity of invasive squamous cell carcinomas (1.6-2.5) was significantly greater than that of actinic keratosis and in situ lesions. Likewise, while the average staining intensity of primary squamous cell carcinomas and metastatic squamous cell carcinomas was not found to be statistically significant (3.1-3.5 and 3.1-3.8, respectively), the average staining intensity of these lesions was significantly higher than that of invasive lesions. We also found that the intensity of matrix metalloproteinase-2 staining correlates with cellular atypia, inflammation, neovascularization, and the invasive tumor front, as well as tumor aggressiveness, and may play a role in the pathogenesis, invasion, and metastasis of cutaneous squamous cell carcinoma.
基质金属蛋白酶构成了一个参与细胞外基质降解的酶家族。肿瘤细胞必须穿透基底膜并穿过细胞外基质，才能侵入周围组织并转移至远处部位。明胶酶，尤其是明胶酶A（基质金属蛋白酶-2），对基底膜成分具有降解活性，可能参与原位鳞状细胞癌病变的进展。基质金属蛋白酶-2的过表达与多种癌症类型的肿瘤侵袭和转移相关，包括黏膜发生的鳞状细胞癌。然而，目前文献中尚未对基质金属蛋白酶-2过表达与皮肤鳞状细胞癌的扩散及预后之间的相关性进行描述。在本研究中，我们采用免疫组织化学技术检测了10例光化性角化病、15例原位、13例浸润性、13例原发性（有记录的转移性疾病）、11例转移性以及8例复发性鳞状细胞癌病例中基质金属蛋白酶-2的表达。我们发现，虽然光化性角化病和原位病变的平均染色强度（0-3+级，3+为最强）无统计学差异（分别为0.87-1.3和0.75-1.4），但浸润性鳞状细胞癌的平均染色强度（1.6-2.5）显著高于光化性角化病和原位病变。同样，虽然原发性鳞状细胞癌和转移性鳞状细胞癌的平均染色强度无统计学差异（分别为3.1-3.5和3.1-3.8），但这些病变的平均染色强度显著高于浸润性病变。我们还发现，基质金属蛋白酶-2染色强度与细胞异型性、炎症、新生血管形成、肿瘤浸润前沿以及肿瘤侵袭性相关，可能在皮肤鳞状细胞癌的发病机制、侵袭和转移中发挥作用。
