Bellahcène A, Castronovo V
Metastasis Research Laboratory, University of Liège, Belgium.
Am J Pathol. 1995 Jan;146(1):95-100.
Microcalcifications are a common phenomenon associated with breast cancer and are often the only mammographic sign of a malignant breast disease. Although microcalcifications are not restricted to breast cancer and can be also associated with benign lesions, it is noteworthy that they are composed exclusively of hydroxyapatite in breast carcinoma. Hydroxyapatite is the bone-associated phosphocalcic crystal the deposition of which in bone tissue requires the coordinated expression of several molecules such as osteonectin (OSN) and osteopontin (OPN), synthesized by cells of the osteoblastic lineage. In this study, we evaluated the expression of these two bone matrix proteins, using an immunoperoxidase technique and specific antibodies, in 79 breast lesions including 28 benign and 51 cancerous specimens. We found that normal mammary tissue associated with the lesions examined expressed generally undetectable or lightly detectable (0 or 1+) amounts of OSN and OPN (92 and 81%, respectively). Benign breast lesions, including fibroadenoma and fibrocystic dysplasia, were generally weakly stained (0 or 1+) with both anti-OSN and anti-OPN antibodies (96.4 and 60.7%, respectively). Interestingly, the majority of both in situ and invasive breast carcinoma lesions showed a strong expression (2+ or 3+) for OSN or OPN (74.5 and 84.3%, respectively). High expression of these two bone matrix proteins was associated with frequent microcalcification deposition in the lesion. This study is the first extensive study of OSN and OPN expression in mammary cancers. Our data suggest that OSN and OPN could play a role in the formation of ectopic microcalcifications often associated with breast cancer. It is also tempting to speculate that the expression of these two glycoproteins by breast cancer cells play a role in the preferred bone homing of breast metastases.
微钙化是与乳腺癌相关的常见现象，通常是乳腺恶性疾病的唯一乳腺X线征象。尽管微钙化并非乳腺癌所特有，也可与良性病变相关，但值得注意的是，在乳腺癌中它们仅由羟基磷灰石组成。羟基磷灰石是与骨相关的磷酸钙晶体，其在骨组织中的沉积需要成骨细胞系细胞合成的几种分子如骨连接蛋白（OSN）和骨桥蛋白（OPN）的协同表达。在本研究中，我们使用免疫过氧化物酶技术和特异性抗体，评估了这两种骨基质蛋白在79例乳腺病变中的表达，其中包括28例良性标本和51例癌性标本。我们发现，与所检查病变相关的正常乳腺组织通常表达不可检测或轻度可检测（分别为0或1+）量的OSN和OPN（分别为92%和81%）。良性乳腺病变，包括纤维腺瘤和纤维囊性增生，用抗OSN和抗OPN抗体染色通常较弱（0或1+）（分别为96.4%和60.7%）。有趣的是，大多数原位和浸润性乳腺癌病变对OSN或OPN显示强表达（2+或3+）（分别为74.5%和84.3%）。这两种骨基质蛋白的高表达与病变中频繁的微钙化沉积相关。本研究是对OSN和OPN在乳腺癌中表达的首次广泛研究。我们的数据表明，OSN和OPN可能在通常与乳腺癌相关的异位微钙化形成中起作用。也很容易推测，乳腺癌细胞对这两种糖蛋白的表达在乳腺转移灶优先归巢至骨中起作用。
