Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy

Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy
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DOI:
10.1007/s00066-019-01468-z
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发表时间:
2019-07-01
影响因子:
3.1
通讯作者:
Sakata, Koh-ichi
Sakata, Koh-ichi
中科院分区:
医学2区
文献类型:
--
作者:
Kitagawa, Mio;Someya, Masanori;Sakata, Koh-ichi

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我们检测了保乳治疗后同侧乳腺癌复发(IBTR)患者的乳腺癌细胞中非同源末端连接(NHEJ)蛋白的表达。我们还研究了肿瘤细胞中nhej相关蛋白的表达在两种类型的IBTR中是否存在差异,即从肿瘤床上再生的真正复发(TR)或新发原发肿瘤(NP)。患者和方法最初的队列包括560例1995年2月至2006年3月期间接受保乳治疗的乳腺癌患者,其中520例无IBTR患者和40例有IBTR患者。采用倾向评分匹配方法,选择40例三人组(120例),其中1例IBTR患者和2例非IBTR患者。对手术标本进行NHEJ相关蛋白的免疫组化检查。结果40例IBTR患者中有22例为TR, 18例为NP。NP患者的15年总生存率为85.9%,TR患者为95.5%,而无IBTR患者的15年总生存率为96.5%。肿瘤细胞中XRCC4高表达患者的IBTR率显著高于XRCC4低表达患者(P < 0.001)。高表达XRCC4的患者发生TR的频率明显高于低表达XRCC4的患者(p < 0.001)。XRCC4在肿瘤细胞中的表达与NP的发生无显著相关性。结论TR引起的IBTR可能与肿瘤细胞放射敏感性低有关,可能与XRCC4高表达有关。
Background We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of anew primary tumor (NP).Patients and methods The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens.Results The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP.Conclusion IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.