Balance of cell proliferation and apoptosis in breast carcinogenesis
Balance of cell proliferation and apoptosis in breast carcinogenesis
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DOI：
10.1023/a:1006396103777
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发表时间：
1999-11-01
影响因子：
3.8
通讯作者：
Baak, JPA
中科院分区：
文献类型：
--
作者：
Mommers, ECM;van Diest, PJ;Baak, JPA
我们通过对乳腺浸润性导管性病变到浸润性癌的分析，确定了有丝分裂和细胞凋亡指数，以寻找乳腺癌发生过程中增殖/细胞死亡平衡的紊乱。研究对象为72例乳腺浸润性癌前病变(非浸润性癌)和103例浸润性乳腺癌。苏木精-伊红染色切片(分别为MI和Al)显微镜下计数有丝分裂细胞和凋亡细胞，计算MI与AI的比值(M/A指数)。根据组织学类型和核分级区分高分化和低分化乳腺病变，得出两种合理的乳腺癌发生发展模型。对于高分化的乳腺病变，增生性病变和高分化DCIS的MI相当，但从DCIS到高分化的浸润性癌的MI增加了6倍。AI保持在同一区间，导致并购指数增长4倍。对于低分化的乳腺病变，从增生型到低分化型DCIS的MI和AI显著增加。从DCIS到低分化浸润性癌，MI显著增加，AI降低2倍(N.S.)，导致M/A指数显著增加2.5倍。综上所述，从高分化前期浸润性癌向高分化浸润性癌过渡过程中细胞数量的净增加伴随着细胞增殖的增加，而不是细胞凋亡的减少，这表明在这些病变中，增殖相关机制在肿瘤的发生和发展中起着最重要的作用。相比之下，在分化较差的乳腺病变中，细胞凋亡减少似乎在肿瘤的发生和发展中也很重要。目前，我们正在收集既往有浸润性病变活检的浸润性乳腺癌患者，以获得更多支持这一假说的直接证据。
We determined the mitotic and apoptotic index through the spectrum of pre-invasive ductal breast lesions to invasive carcinoma in search of disturbances in the proliferation/cell death balance in breast carcinogenesis. Seventy-two pure pre-invasive ductal breast lesions (without invasive carcinoma) and 103 invasive breast carcinomas were used. The numbers of mitotic and apoptotic cells were microscopically counted in hematoxylin and eosin stained sections (MI and Al, respectively), and the ratio of the values of MI and AI was calculated for each individual case (M/A index).A distinction was made between well differentiated and poorly differentiated breast lesions, based on histological type and nuclear grade, to arrive at two plausible progression models for breast carcinogenesis. For the well differentiated breast lesions, the MI was rather equal for hyperplasias and well differentiated DCIS, but increased 6-fold from DCIS to well differentiated invasive carcinoma. The AI remained in the same range, resulting in a 4-fold increase of the M/A index. For the poorly differentiated breast lesions, a significant increase in MI and AI was found from hyperplasia to poorly differentiated DCIS. From DCIS to poorly differentiated invasive carcinoma, the MI increased significantly and the AI decreased 2-fold (n.s.), resulting in a 2.5-fold significant increase of the M/A index.In conclusion, the net increase of the number of cells in the transition from well differentiated pre-invasive to well differentiated invasive carcinoma is accompanied by an increase of cell proliferation rather than decrease in apoptosis, suggesting that in these lesions, proliferation related mechanisms are most important in carcinogenesis and progression. In contrast, in poorly differentiated breast lesions, decreased apoptosis seems to be also important in carcinogenesis and progression. At present, we are gathering patients with invasive breast cancer who had a previous biopsy with a pre-invasive lesion to obtain further more direct evidence for this hypothesis.