Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers
Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers
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DOI：
10.1016/j.clbc.2020.02.008
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发表时间：
2020-08-01
影响因子：
3.1
通讯作者：
Gatalica, Zoran
中科院分区：
文献类型：
--
作者：
Vranic, Semir;Stafford, Phillip;Gatalica, Zoran
梭形细胞癌是一种罕见的化生性乳腺癌亚型，具有三阴性表型。使用免疫组织化学和 DNA/RNA 测序对 23 种梭形细胞癌进行了免疫肿瘤学和靶向治疗的生物标志物的全面探索。大多数情况下，梭形细胞癌的特点是可靶向的分子改变，但由于缺乏统一的研究结果，有必要对患者进行个体分析。简介：梭形细胞癌是化生性乳腺癌的一种罕见亚型，具有三阴性（TNBC：雌激素受体阴性/孕激素受体阴性/人表皮生长因子受体2阴性）表型。它与对传统化疗的显着耐药性有关，并且总体预后较差。材料和方法：使用免疫组织化学和 DNA/RNA 测序对 23 例纯乳腺梭形细胞癌（18 例原发性和 5 例复发/转移性）进行了免疫肿瘤学和靶向治疗的生物标志物的全面探索。结果：大多数（21/23）梭形细胞癌是 TNBC。各 2 例检测到雌激素和雄激素受体表达高于治疗阈值。 23 例中有 21 例发现致病基因突变，包括 PIK3CA、TP53、HRAS、NF1 和 PTEN。一名化疗前和化疗后样本相匹配的病例在两个样本中表现出一致的突变谱（PIK3CA 和 HRAS 突变）。 5例存在基因扩增，其中1例未检测到突变。梭形细胞癌队列的总突变负荷始终较低（整个 TNBC 队列均低于第 80 个百分位）。所有肿瘤都是微卫星稳定的。在肿瘤细胞（7/21 例）和肿瘤浸润免疫细胞（2/21 例）中均观察到程序性死亡配体 1 表达。结论：大多数病例中梭形细胞癌的特点是可靶向的分子改变，但由于缺乏统一的发现，因此有必要对患者进行个体分析。检测单个生物标志物组合应该可以改善这种罕见但侵袭性疾病的治疗选择。 (C) 2020 作者。由爱思唯尔公司出版
Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative phenotype. Twenty-three spindle cell carcinomas were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but, owing to the lack of uniform findings, individual patient profiling is necessary.Introduction: Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It is associated with a marked resistance to conventional chemotherapy and has an overall poor outcome. Materials and Methods: Twenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. Results: The majority (21/23) of spindle cell carcinomas were TNBC. Estrogen and androgen receptor expression above the therapeutic thresholds were detected in 2 cases each. Pathogenic gene mutations were identified in 21 of 23 cases, including PIK3CA, TP53, HRAS, NF1, and PTEN. One case with matched pre- and post-chemotherapy samples exhibited a consistent mutational profile (PIK3CA and HRAS mutations) in both samples. Gene amplifications were present in 5 cases, including 1 case without detectable mutations. The spindle cell carcinomas cohort had consistently low total mutational burden (all below the 80th percentile for the entire TNBC cohort). All tumors were microsatellite stable. Programmed death-ligand 1 expression was observed on both tumor cells (in 7/21 cases), and in tumor-infiltrating immune cells (2/21 cases). Conclusions: Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but owing to the lack of uniform findings, individual patient profiling is necessary. Detection of individual combinations of biomarkers should improve treatment options for this rare but aggressive disease. (C) 2020 The Author(s). Published by Elsevier Inc.