Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Gelre Hospitals, Apeldoorn, The Netherlands.
Mod Pathol. 2018 Dec;31(12):1816-1833. doi: 10.1038/s41379-018-0099-2. Epub 2018 Jul 5.
Columnar cell lesions have been proposed as precursor lesions of low-grade breast cancer. The molecular characteristic of low-grade breast neoplasia is whole-arm loss of chromosome 16q. Copy number changes of 6 genes on 16p and 20 genes on 16q were analysed by multiplex ligation-dependent probe amplification in 165 lesions of 103 patients. Twenty-three columnar cell lesions and 19 atypical ducal hyperplasia lesions arising in columnar cell lesions were included, as well as cases of usual ductal hyperplasia, blunt duct adenosis, ductal carcinoma in situ, lobular neoplasia and invasive carcinoma. Usual ductal hyperplasia and blunt duct adenosis lacked whole-arm losses of 16q. In contrast, columnar cell lesions without atypia, columnar cell lesions with atypia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ and low-grade invasive carcinomas increasingly harboured whole-arm losses of 16q (17%, 27%, 47% and 57%, respectively). However, no recurrent losses in specific genes could be identified. In several patients, columnar cell lesions and atypical ductal hyperplasia harboured similar losses as related ductal carcinoma in situ or invasive carcinomas within the same breast. There were indications for 16q breakpoints near the centromere. Whole-arm gains on 16p were relatively scarce and there was no relation between whole-arm gains of 16p and progression of lesions of the low-grade breast neoplasia family. In conclusion, columnar cell lesions (with and without atypia) often harbour whole-arm losses of 16q, which underlines their role as precursors in low-grade breast carcinogenesis, in contrast with usual ductal hyperplasia and blunt duct adenosis. However, no recurrent losses in specific genes could be identified, pointing to minor events in multiple tumour suppressor genes rather than major events in a single 16q gene contributing to low-grade breast carcinogenesis.
柱状细胞病变被认为是低级别乳腺癌的前体病变。低级别乳腺肿瘤的分子特征是整条 16 号染色体长臂缺失。在 103 名患者的 165 个病变中，通过多重连接依赖性探针扩增分析了 16p 上的 6 个基因和 16q 上的 20 个基因的拷贝数变化。研究包括 23 例柱状细胞病变和 19 例起源于柱状细胞病变的非典型导管增生病变，以及普通导管增生、钝性导管腺病、导管原位癌、小叶肿瘤和浸润性癌。普通导管增生和钝性导管腺病缺乏整条 16q 的缺失。相比之下，无非典型性的柱状细胞病变、有非典型性的柱状细胞病变、非典型导管增生、低级别导管原位癌和低级别浸润性癌越来越多地出现整条 16q 的缺失（分别为 17%、27%、47%和 57%）。然而，没有发现特定基因的重复缺失。在一些患者中，柱状细胞病变和非典型导管增生与同一乳房内相关的导管原位癌或浸润性癌具有相似的缺失。存在靠近着丝粒的 16q 断裂点的迹象。16p 上的整条染色体增益相对较少，并且 16p 上的整条染色体增益与低级别乳腺肿瘤家族病变的进展之间没有关系。总之，柱状细胞病变（有或无非典型性）常携带整条 16q 的缺失，这突出了它们在低级别乳腺癌发生中的前体作用，与普通导管增生和钝性导管腺病形成对比。然而，没有发现特定基因的重复缺失，这表明在多个肿瘤抑制基因中发生了较小的事件，而不是在单个 16q 基因中发生了较大的事件，从而导致了低级别乳腺癌的发生。
