Castronovo V, Bellahcene A
Metastasis Research Laboratory, Tour de Pathologie, -1, Bat B23, Sart-Tilman, Liege, 4000, Belgium.
Int J Oncol. 1998 Feb;12(2):305-8. doi: 10.3892/ijo.12.2.305.
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.
微钙化常常与人类乳腺的良性和恶性病变相关。大约40%的乳腺癌存在这种异位矿化，而且通常情况下，它们是乳腺钼靶检查中唯一提示肿瘤性病变存在的特征。与乳腺癌相关的微钙化通常由骨特异性矿物质羟基磷灰石组成。乳腺恶性组织中此类晶体形成的机制尚未阐明。最近有证据表明乳腺癌细胞表达多种骨基质蛋白，包括骨连接蛋白、骨桥蛋白和骨唾液蛋白（BSP），这可能提供了一条线索。后一种磷蛋白参与羟基磷灰石结晶的起始过程，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例以存在微钙化和高表达BSP为特征的人类乳腺癌病变。对这些病变的组织学检查在大多数病例中提示，微钙化是矿化的乳腺癌细胞。苏木精染成蓝色的羟基磷灰石似乎集中在单个或相关癌细胞周围。用特异性标记DNA的4',6-二脒基-2-苯基吲哚对这些组织切片进行染色，使我们证实矿化结构中含有细胞。这些数据首次直接证明乳腺微钙化是癌细胞的化石。这种现象的机制仍有待证实。我们推测BSP的高表达可能为钙和磷酸盐结晶形成羟基磷灰石创造了合适的微环境。
