Laé Marick, Vincent-Salomon Anne, Savignoni Alexia, Huon Isabelle, Fréneaux Paul, Sigal-Zafrani Brigitte, Aurias Alain, Sastre-Garau Xavier, Couturier Jérôme
Département de Biologie des Tumeurs, Service de Pathologie, Institut Curie-Hôpital, Paris, France.
Mod Pathol. 2007 Apr;20(4):435-44. doi: 10.1038/modpathol.3800756. Epub 2007 Mar 2.
Phyllodes tumors are rare fibroepithelial tumors of the breast. The pathologic grading of phyllodes tumors based on the aspect of the stromal component, is divided into 2 or 3 grades according to the system used. To determine whether genetic markers could be of use for improving the classification of phyllodes tumors and to provide a better knowledge of the genetic alterations in these tumors, we analyzed chromosomal changes detected by comparative genomic hybridization (CGH) in comparison with histological data, in a series of 30 cases. Recurrent chromosome imbalances were observed in 55, 91 and 100% of benign, borderline and malignant phyllodes tumors, respectively. The mean number of chromosome changes was one in benign, six in borderline, and six in malignant phyllodes tumors. Most frequent genetic imbalances were +1q (12/30), -13q (7/30), -6q (9/30), +5 (9/30) and -10p (8/30). Gains of 1q, present in only one of nine benign tumors, were found in 11/21 (51%) borderline or malignant tumors. Losses of 13q have 13q14.2 as smallest region of overlap, suggesting that the RB1 gene could be the target of deletions. Amplifications of 12q14, involving the MDM2 locus, and of 8p24, involving the MYC gene, were observed in one case each. Borderline and malignant phyllodes tumors could not be differentiated on the basis of their genomic imbalances (presence and number of chromosomal changes, presence of 1q gain and/or 13q loss). Conversely, benign tumors could be significantly differentiated from the group composed of borderline and malignant tumors (P<0.01). This study reveals two distinct patterns of genomic imbalance in phyllodes tumors: benign, with none or a few chromosome changes and malignant, with numerous recurrent chromosomal changes, in particular 1q gain and 13q loss. Helpful additional pathological criteria for differentiating the two genetic groups of phyllodes tumors are the nuclear size and the mitotic rate.
叶状肿瘤是一种罕见的乳腺纤维上皮性肿瘤。根据间质成分的表现对叶状肿瘤进行病理分级，根据所使用的系统可分为2级或3级。为了确定基因标志物是否有助于改进叶状肿瘤的分类，并更好地了解这些肿瘤中的基因改变，我们分析了30例病例中通过比较基因组杂交（CGH）检测到的染色体变化，并与组织学数据进行了比较。分别在55%、91%和100%的良性、交界性和恶性叶状肿瘤中观察到复发性染色体失衡。良性叶状肿瘤的平均染色体变化数为1个，交界性为6个，恶性为6个。最常见的基因失衡为+1q（12/30）、-13q（7/30）、-6q（9/30）、+5（9/30）和-10p（8/30）。1q增益仅在9例良性肿瘤中的1例中出现，在11/21（51%）的交界性或恶性肿瘤中发现。13q缺失的最小重叠区域为13q14.2，提示RB1基因可能是缺失的靶点。分别在1例病例中观察到涉及MDM2基因座的12q14扩增和涉及MYC基因的8p24扩增。交界性和恶性叶状肿瘤不能根据其基因组失衡（染色体变化的存在和数量、1q增益和/或13q缺失的存在）进行区分。相反，良性肿瘤可与由交界性和恶性肿瘤组成的组显著区分（P<0.01）。本研究揭示了叶状肿瘤基因组失衡的两种不同模式：良性模式，无或仅有少数染色体变化；恶性模式，有大量复发性染色体变化，特别是1q增益和13q缺失。区分叶状肿瘤两个基因组的有用的额外病理标准是核大小和有丝分裂率。
