Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea.
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea.
Breast Cancer Res Treat. 2020 Oct;183(3):697-704. doi: 10.1007/s10549-020-05811-2. Epub 2020 Jul 26.
Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) is implicated in anti-viral immune response and cancer mutagenesis. Germline APOBEC3B deletion is associated with increased susceptibility to breast cancer. We aimed to evaluate the association between germline APOBEC3B deletion and clinical phenotypes of breast cancer in Korean patients with operable breast cancer.
Mononuclear blood cell DNA of 103 patients with operable breast cancer was collected at Seoul National University Bundang Hospital in 2009. The DNA was sequenced to analyze APOBEC3B deletion status. Further, tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor cells were measured using immunohistochemistry.
Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3B), one-one copy deletion (A3B), and no deletion (A3B), respectively. For other cancer susceptibility gene alterations, 9 (8.7%) patients were identified as pathogenic variants: RAD51D (n = 1), GJB2 (n = 1), BRCA1 (n = 1), BRCA2 (n = 2), ATM (n = 1), USH2A (n = 1), RET (n = 1), BARD1 (n = 1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer, such as age, family history of cancer, and bilateral breast cancer. Further, according to follow-up observations, APOBEC3B deletion was not predictive of disease-free survival. In ER+ subtype, a trend toward better survival was observed in patients with A3B genotype as compared to patients with A3B and A3B genotype (log-rank, P = 0.25). In patients with sufficient tumor samples for the assessment of TIL (n = 63) and PD-L1 (n = 71), the A3B genotype was significantly associated with high TILs (> 10%) than other tumor genotypes (6/7 patients in A3B vs. 13/24 in A3B vs. 15/32 in A3B: Fisher's exact test, P = 0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients > 1% PD-L1 in A3B vs. 4/26 in A3B vs. 8/38 in A3B: P = 0.901).
We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3B genotype and high TILs suggests that patients carrying this genotype could be potential candidates for immunotherapy.
载脂蛋白 B mRNA 编辑酶、催化多肽样 3B（APOBEC3B）参与抗病毒免疫反应和癌症诱变。种系 APOBEC3B 缺失与乳腺癌易感性增加有关。我们旨在评估韩国可手术乳腺癌患者中种系 APOBEC3B 缺失与乳腺癌临床表型之间的关联。
2009 年，在首尔国立大学盆唐医院收集了 103 名可手术乳腺癌患者的单核血细胞 DNA。对 DNA 进行测序以分析 APOBEC3B 缺失状态。进一步，使用免疫组织化学法测量肿瘤浸润淋巴细胞（TIL）和肿瘤细胞中程序性细胞死亡配体 1（PD-L1）的表达。
中位乳腺癌诊断年龄为 46（25-72）岁。在 APOBEC3B 缺失分析中，10（9.7%）、36（35.0%）和 57（55.3%）名患者分别被鉴定为 2 拷贝缺失（A3B）、1 拷贝缺失（A3B）和无缺失（A3B）。对于其他癌症易感性基因改变，9（8.7%）名患者被鉴定为致病性变异：RAD51D（n=1）、GJB2（n=1）、BRCA1（n=1）、BRCA2（n=2）、ATM（n=1）、USH2A（n=1）、RET（n=1）、BARD1（n=1）。我们观察到种系 APOBEC3B 缺失与乳腺癌的任何临床病理特征均无显著关联，例如年龄、癌症家族史和双侧乳腺癌。此外，根据随访观察，APOBEC3B 缺失不能预测无病生存。在 ER+亚型中，与 A3B 和 A3B 基因型相比，A3B 基因型的患者生存趋势更好（对数秩检验，P=0.25）。在有足够肿瘤样本评估 TIL（n=63）和 PD-L1（n=71）的患者中，A3B 基因型与高 TILs（>10%）显著相关，而其他肿瘤基因型则不相关（A3B 中 6/7 例患者 vs. A3B 中 13/24 例患者 vs. A3B 中 15/32 例患者：Fisher 确切检验，P=0.029）。然而，PD-L1 表达与 APOBEC3B 缺失状态无关（A3B 中 1/7 例患者>1% PD-L1 与 A3B 中 4/26 例患者 vs. A3B 中 8/38 例患者：P=0.901）。
我们在 9.7%的韩国可手术乳腺癌患者中发现了种系 APOBEC3B 缺失。A3B 基因型与高 TILs 之间的关系表明，携带这种基因型的患者可能是免疫治疗的潜在候选者。
