Evidence that breast cancer associated microcalcifications are mineralized malignant cells.
Evidence that breast cancer associated microcalcifications are mineralized malignant cells.
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DOI：
10.3892/ijo.12.2.305
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发表时间：
1998-02
影响因子：
5.2
通讯作者：
Vincenzo Castronovo;A. Bellahcène
中科院分区：
文献类型：
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作者：
Vincenzo Castronovo;A. Bellahcène
微钙化通常与人类乳房的良性和恶性病变有关。大约40%的乳腺癌存在这种异位矿化，通常，它们是唯一表明肿瘤病变存在的乳房X线特征。与乳腺癌相关的微钙化通常由羟基磷灰石组成，羟基磷灰石是一种骨骼特有的矿物。在乳腺恶性组织中形成这种晶体的机制尚未阐明。最近的研究表明，乳腺癌细胞表达多种骨基质蛋白，包括骨连蛋白、骨桥蛋白和骨涎蛋白(BSP)，这可能提供了线索。后者参与了羟基磷灰石结晶的启动，其在乳腺癌中的表达与羟基磷灰石微钙化的存在有关。我们检查了10个以微钙化和BSP高表达为特征的人类乳腺癌病变。组织学检查表明，在大多数病例中，微钙化是乳腺癌细胞的矿化。苏木素染成蓝色的羟基磷灰石似乎集中在单个相关的癌细胞周围。用4‘，6-二氨基-2-苯基吲哚对这些组织切片进行染色后，我们发现矿化的结构中含有细胞。这些数据首次直接证明乳房微钙化是癌细胞的化石。造成这种现象的机制尚待证实。我们推测，BSP的高表达可能为钙和磷结晶成羟基磷灰石创造了合适的微环境。
Microcalcifications are often associated with both benign and malignant human breast lesions. Around 40% of mammary carcinoma present such ectopic mineralization and frequently, they are the only mammographic feature that indicate the presence of a tumoral lesion. Microcalcifications associated with breast cancer are usually composed of hydroxyapatite, the bone specific mineral. The mechanisms responsible for the formation of such crystals within breast malignant tissue have not been elucidated. A possible clue could be provided by the recent demonstration that breast cancer cells express several bone matrix proteins including osteonectin, osteopontin and bone sialoprotein (BSP). This latter phospho-protein is involved in the initiation of hydroxyapatite crystallisation and its expression in breast cancer has been associated to the presence of hydroxyapatite microcalcifications. We examined 10 human breast cancer lesions which were characterized by the presence of microcalcifications and high expression of BSP. Histological examination of the lesions suggested, in most of the cases, that the microcalcifications were breast cancer cells which became mineralized. Hydroxyapatite stained in blue by hematoxylin appears concentrated around single of associated cancer cells. Staining of these tissue sections with 4',6 diamidino-2-phenylindole which specifically labels DNA led us to demonstrate that the mineralizated structures contain cells. These data are the first direct demonstration that breast microcalcifications are fossils of cancer cells. The mechanisms for such a phenomenon remain to be demonstrated. We speculate that the high expression of BSP could create an appropriate microenvironment for the crystallisation of calcium and phosphate into hydroxyapatite.