皮肤转移（CM）占乳腺癌（BC）患者的5-30%，治疗反应不佳且预后不良。更好地了解转移中涉及的分子改变至关重要，这将有助于确定 CM 的诊断和疗效生物标志物。我们回顾性审查了总共 13 名组织学或细胞学诊断为乳腺癌和 CM 的患者。从医疗记录中提取临床信息。使用 425 个癌症相关基因的下一代测序 (NGS) 分析匹配的原发肿瘤及其淋巴结或 CM 组织的突变情况。所有组织也通过免疫组织化学（IHC）进行分析。还评估了预后与各种临床和分子因素的关联。超过一半的患者Ki67低（< 50%，53.7%）。大多数患者（12 例，92.3%）有皮肤以外的其他转移部位。从诊断到出现 CM (T1) 的中位时间为 15 个月（范围：0-94 个月），从 CM 到死亡 (T2) 的中位时间为 13 个月（范围 1-78）。三种组织中最常改变的基因是 TP53 (69.6%, 16/23)、PIK3CA (34.8%, 8/23) 和 MYC (26.1%)。 CM 中的改变数量往往高于原发肿瘤（中位数 8 比 6，P = 0.077）。 STK11 中的拷贝数丢失、FGFR4、TERT、AR、FLT4 和 VEGFA 中的拷贝数增加以及 ATRX、SRC、AMER1 和 RAD51C 中的突变在 CM 中显着富集（所有 P<0.05）。 Ki67 高组（> 50%）的 T1 显着短于 Ki67 低组（≤ 50%）（中位 12.5 个月与 50.0 个月，P = 0.036）。 TP53、PIK3CA 突变和 TERT 扩增组与 T2 较差相关（中位时间分别为 11 个月与 36 个月，P = 0.065；8 个月与 36 个月，P = 0.013；中位 7 个月与 36 个月，P = 0.003）。所有p值均未调整。我们比较了原发性乳腺癌组织与其相应CM组织的基因组特征，并讨论了可能导致晚期乳腺癌患者皮肤转移的潜在基因和途径。 TP53、PIK3CA 突变体和 TERT 扩增可作为 CM 患者预后不良的生物标志物。© 2024。作者。

Cutaneous metastasis (CM) accounts for 5-30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM.We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated.More than half of the patients were Ki67 low (< 50%, 53.7%). Most patients (12, 92.3%) had other metastasis sites other than skin. The median time from diagnosis to the presentation of CM (T1) was 15 months (range: 0-94 months) and the median time from CM to death (T2) was 13 months (range 1-78). The most frequently altered genes across the three types of tissues were TP53 (69.6%, 16/23), PIK3CA (34.8%, 8/23), and MYC (26.1%). The number of alterations in CM tends to be higher than in primary tumors (median 8 vs. 6, P = 0.077). Copy number loss in STK11, copy number gain in FGFR4, TERT, AR, FLT4 and VEGFA and mutations in ATRX, SRC, AMER1 and RAD51C were significantly enriched in CM (all P < 0.05). Ki67 high group (> 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted.We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.© 2024. The Author(s).