Prognostic significance of CD117 expression and TP53 missense mutations in triple-negative breast cancer.
Prognostic significance of CD117 expression and TP53 missense mutations in triple-negative breast cancer.
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CD117表达和TP53错义突变在三阴性乳腺癌中的预后意义
DOI：
10.3892/ol.2018.8104
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发表时间：
2018-05
期刊：
影响因子：
2.9
通讯作者：
Liu G
中科院分区：
文献类型：
--
作者：
Luo Y;Huang W;Zhang H;Liu G
三阴性乳腺癌（TNBC）侵袭性极强，预后较差。目前尚未发现三阴性乳腺癌已知的预测或预后标志物。已有研究表明，在人类大肠癌细胞中，抑制肿瘤蛋白P53（TP53）可提高分化簇117（CD117）的水平。然而，据我们所知，TP53在三阴性乳腺癌中对CD117的调控作用尚未见报道。在本研究中，我们探究了CD117蛋白表达与TP53突变之间的关联，并评估了它们在三阴性乳腺癌患者中的预后价值。
我们共检测了58例三阴性乳腺癌和48例非三阴性乳腺癌组织样本中CD117、p53的表达情况以及TP53突变情况。通过免疫组织化学方法检测增殖标志物Ki - 67（MKI67）的增殖指数和血管侵犯指数（通过检测D2 - 40和CD34获得），并采用直接测序法检测TP53基因4 - 8号外显子的突变情况。对CD117与p53水平或TP53突变及临床参数之间的关联进行统计学评估。
结果显示，三阴性乳腺癌患者中CD117或MKI67阳性率、CD117 + /TP53错义突变 + 率、TP53错义突变率或复发率均显著高于非三阴性乳腺癌患者。在三阴性乳腺癌组织中，CD117的存在与TP53错义突变（P = 0.031）、血管侵犯、复发及MKI67相关。CD117 + /TP53错义突变 + 也与血管侵犯、复发及MKI67相关。单因素分析表明，MKI67、血管侵犯、CD117、CD117 + /TP53错义突变 + 以及TP53错义突变与三阴性乳腺癌患者的总生存期相关。多因素分析显示，原发性肿瘤中的血管侵犯和CD117 + /TP53错义突变 + 是三阴性乳腺癌患者的独立预后因素。
综上所述，CD117 + /TP53错义突变 + 与三阴性乳腺癌中的MKI67、血管侵犯和肿瘤复发相关。原发性肿瘤中同时存在CD117和TP53错义突变是三阴性乳腺癌患者生存的独立预后因素。
Triple-negative breast cancer (TNBC) is extremely aggressive and associated with poor prognosis. There are no known predictive or prognostic markers for TNBC. Inhibition of tumor protein P53 (TP53) has been demonstrated to increase the levels of cluster of differentiation 117 (CD117) in human colorectal cancer cells. However, the function of TP53 in the regulation of CD117 in TNBC has, to the best of our knowledge, not been reported. In the present study, the association between the expression of CD117 protein and TP53 mutations was investigated, and their prognostic value in patients with TNBC was assessed. A total of 58 TNBC and 48 non-TNBC breast cancer tissue samples were assessed for the expression of CD117, p53 and TP53 mutations. The marker of proliferation Ki-67 (MKI67) proliferation index and vascular invasion index (obtained by measuring D2-40 and CD34) was investigated via immunohistochemistry, and mutations in exons 4–8 of TP53 were measured using direct sequencing. Associations between CD117 and p53 levels or TP53 mutations and clinical parameters were statistically evaluated. The rates of CD117 or MKI67 positivity, CD117+/TP53 missense mutation+, TP53 missense mutations or recurrence were significantly higher in patients with TNBC than in patients with non-TNBC. In TNBC tissues, the presence of CD117 was associated with TP53 missense mutations (P=0.031), vascular invasion, recurrence and MKI67. CD117+/TP53 missense mutation+ also associated with vascular invasion, recurrence and MKI67. Under univariate analysis, MKI67, vascular invasion, CD117, CD117+/TP53 missense mutation+ and TP53 missense mutations were associated with the overall survival of patients with TNBC. Multivariate analysis revealed that vascular invasion and CD117+/TP53 missense mutation+ in primary tumors were independent prognostic factors in patients with TNBC. In conclusion, CD117+/TP53 missense mutation+ was associated with MKI67, vascular invasion and tumor recurrence in TNBC. The presence of CD117 and TP53 missense mutations together in the primary tumors was an independent prognostic factor for survival of patients with TNBC.
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影响因子：
2.4
作者：
Kim HW;Lee HM;Hwang SH;Ahn SG;Lee KA;Jeong J
通讯作者：
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影响因子：
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Fountzilas G;Giannoulatou E;Alexopoulou Z;Zagouri F;Timotheadou E;Papadopoulou K;Lakis S;Bobos M;Poulios C;Sotiropoulou M;Lyberopoulou A;Gogas H;Pentheroudakis G;Pectasides D;Koutras A;Christodoulou C;Papandreou C;Samantas E;Papakostas P;Kosmidis P;Bafaloukos D;Karanikiotis C;Dimopoulos MA;Kotoula V
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影响因子：
11.5
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通讯作者：
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作者：
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