Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Breast Cancer. 2022 Mar;29(2):216-223. doi: 10.1007/s12282-021-01301-5. Epub 2021 Oct 8.
Deletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration.
We made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysis RESULTS: Heterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade (p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity (p = 0.0182), high Ki67 proliferation index (p < 0.0001), amplifications of HER2 (p = 0.0159), CCND1 (p = 0.0069), and cMYC (p = 0.0411), as well as deletions of PTEN (p = 0.0003), 8p21 (p < 0.0001), and 9p21 (p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases.
Our data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.
已报道涉及 6 号染色体长臂的缺失发生在乳腺癌中,但对于这种改变的临床相关性知之甚少。
我们利用了一个预先存在的包含 2197 例乳腺癌的组织微阵列,并使用 6q15/着丝粒 6 双标记探针进行荧光原位杂交(FISH)分析。
在可解释的 1099 例癌症中,发现杂合性 6q15 缺失 202 例(18%),其中无特殊类型(NST)癌症占 19%,29 例小叶癌占 3%,41 例筛状癌占 7%,18 例具有乳头状特征的癌症占 28%。未检测到纯合性缺失。在最大的 NST 肿瘤亚组中,6q15 缺失与晚期肿瘤分期和高级别显著相关(均为 p<0.0001)。6q 缺失还与雌激素受体阴性(p=0.0182)、高 Ki67 增殖指数(p<0.0001)、HER2(p=0.0159)、CCND1(p=0.0069)和 cMYC(p=0.0411)扩增以及 PTEN(p=0.0003)、8p21(p<0.0001)和 9p21(p=0.0179)缺失相关。然而,在所有癌症、NST 癌症或存在或不存在淋巴结转移的癌症亚组中,6q15 缺失与患者生存均无关。
我们的数据表明,6q 缺失是乳腺癌中的常见事件,与不良的肿瘤表型和基因组不稳定性特征具有统计学关联。没有任何预后影响表明 6q15 缺失检测在乳腺癌患者中没有临床应用价值。