Buerger H, Otterbach F, Simon R, Schäfer K L, Poremba C, Diallo R, Brinkschmidt C, Dockhorn-Dworniczak B, Boecker W
Gerhard-Domagk-Institute of Pathology, University of Münster, Germany.
J Pathol. 1999 Dec;189(4):521-6. doi: 10.1002/(SICI)1096-9896(199912)189:4<521::AID-PATH472>3.0.CO;2-B.
Invasive breast cancer shows a wide range of morphological differentiation, associated with differences in prognosis, but as yet, the underlying genetic mechanisms cannot be accounted for. In order to establish a model of the possible progression from the different subtypes of ductal carcinoma in situ (DCIS) to invasive breast cancer, 77 selected cases of invasive breast cancer representing distinct morphological subtypes were investigated by means of comparative genomic hybridization (CGH). There was a high degree of genetic homology between tubular and tubulo-lobular carcinoma and well-differentiated DCIS, and between ductal invasive carcinoma G3 and poorly differentiated DCIS. Highly differentiated invasive breast cancers were characterized by a loss of 16q and a low average number of aberrations per case. In high-grade tumours, losses of this chromosomal region were seen with a much lower frequency in cases with evidence of an aneuploid tumour status. These data demonstrate the close genetic similarity of well-, intermediately, and poorly differentiated DCIS and distinct morphological types of invasive breast carcinoma, providing further evidence that DCIS is a direct precursor lesion of invasive breast cancer and that various evolutionary genetic pathways exist.
浸润性乳腺癌表现出广泛的形态学分化，与预后差异相关，但迄今为止，其潜在的遗传机制尚不清楚。为了建立从不同亚型的导管原位癌（DCIS）到浸润性乳腺癌可能进展的模型，通过比较基因组杂交（CGH）研究了77例代表不同形态学亚型的浸润性乳腺癌病例。管状和小管-小叶癌与高分化DCIS之间，以及导管浸润性癌G3与低分化DCIS之间存在高度的遗传同源性。高分化浸润性乳腺癌的特征是16q缺失和每例平均畸变数量低。在高级别肿瘤中，在有非整倍体肿瘤状态证据的病例中，该染色体区域缺失的频率要低得多。这些数据证明了高分化、中分化和低分化DCIS与浸润性乳腺癌不同形态学类型之间密切的遗传相似性，进一步证明DCIS是浸润性乳腺癌的直接前驱病变，并且存在各种进化遗传途径。
