Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue.
Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue.
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发表时间：
1990-03
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通讯作者：
C. Monteagudo;M. Merino;Josefina;San-Juan;L. Liotta;W. Stetler-Stevenson
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作者：
C. Monteagudo;M. Merino;Josefina;San-Juan;L. Liotta;W. Stetler-Stevenson
在几个实验模型中，肿瘤细胞产生IV型胶原酶与其转移潜能有关。该酶在基底膜IV型胶原周转中的作用也已被提出。针对人类IV型胶原酶的氨基末端(H1)或内部活性部位区域(金属结合区[MBR])的两种新近开发的亲和纯化单特异性抗体，用于福尔马林固定的、石蜡包埋的55例乳腺组织标本的亲和素-生物素-免疫过氧化物酶技术。正常组织和增生性病变组织中肌上皮细胞胞浆免疫染色较强，导管内癌组织中肌上皮细胞胞浆免疫染色不连续。腔上皮细胞在大中型导管中呈阴性或弱阳性，而在正常的末端导管和增生性病变中反应频繁。23例导管内癌中有20例上皮细胞呈免疫反应阳性。40例浸润性癌中36例阳性，12例中10例淋巴结转移细胞阳性。这些结果支持IV型胶原酶在正常乳腺基底膜重塑中的作用。我们的发现表明，肌上皮细胞在这种酶活性中起着关键作用。浸润性癌的高阳性细胞百分率和淋巴结转移的强烈免疫反应性支持了该酶在肿瘤侵袭和转移中的作用，并提示肿瘤细胞是该酶在这些过程中的重要来源。
Production of type IV collagenase by tumor cells has been linked to their metastatic potential in several experimental models. A possible role for this enzyme in basement membrane type IV collagen turnover has also been suggested. Two recently developed affinity-purified, monospecific antibodies directed against the amino terminus (H1), or an internal active site domain (metal binding region [MBR]) of human type IV collagenase, were employed in the avidin-biotin-immunoperoxidase technique in formalin-fixed, paraffin-embedded breast tissue samples from 55 patients. Intense cytoplasmic immunostaining of myoepithelial cells was found in normal and hyperplastic tissue, and discontinuous staining was noted in intraductal carcinomas. Luminal epithelial cells were negative or weakly positive in large- or medium-sized ducts but reacted frequently in normal terminal ducts and hyperplastic lesions. Epithelial cells in intraductal carcinomas exhibited immunoreactivity in 20 of 23 cases. Invasive carcinomas were positive in 36 of 40 cases, and metastatic cells in lymph nodes stained in 10 of 12 cases. These results support a role for type IV collagenase in the basement membrane remodeling of normal breast. Our findings suggest that myoepithelial cells play a pivotal role in this enzymatic activity. The high percentage of positive cells in invasive carcinomas and the strong immunoreactivity of lymph node metastases support the role of the enzyme in tumor invasion and metastasis and suggest that tumor cells are the essential source of the enzyme in these processes.