Luo Yanli, Huang Wentao, Zhang Huizhen, Liu Guang
Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Department of Vascular Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, P.R. China.
Oncol Lett. 2018 May;15(5):6161-6170. doi: 10.3892/ol.2018.8104. Epub 2018 Feb 22.
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 () has been demonstrated to increase the levels of cluster of differentiation 117 (CD117) in human colorectal cancer cells. However, the function of 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 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 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 were measured using direct sequencing. Associations between CD117 and p53 levels or mutations and clinical parameters were statistically evaluated. The rates of CD117 or MKI67 positivity, CD117/ missense mutation, 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 missense mutations (P=0.031), vascular invasion, recurrence and MKI67. CD117/ missense mutation also associated with vascular invasion, recurrence and MKI67. Under univariate analysis, MKI67, vascular invasion, CD117, CD117/ missense mutation and missense mutations were associated with the overall survival of patients with TNBC. Multivariate analysis revealed that vascular invasion and CD117/ missense mutation in primary tumors were independent prognostic factors in patients with TNBC. In conclusion, CD117/ missense mutation was associated with MKI67, vascular invasion and tumor recurrence in TNBC. The presence of CD117 and missense mutations together in the primary tumors was an independent prognostic factor for survival of patients with TNBC.
三阴性乳腺癌（TNBC）极具侵袭性，且预后较差。目前尚无已知的TNBC预测或预后标志物。在人结肠癌细胞中，已证实抑制肿瘤蛋白P53可增加分化簇117（CD117）的水平。然而，据我们所知，P53在TNBC中对CD117调控的功能尚未见报道。在本研究中，我们调查了CD117蛋白表达与P53突变之间的关联，并评估了它们在TNBC患者中的预后价值。共对58例TNBC和48例非TNBC乳腺癌组织样本进行了CD117、p53表达及P53突变检测。通过免疫组化研究增殖标志物Ki-67（MKI67）增殖指数和血管侵袭指数（通过检测D2-40和CD34获得），并使用直接测序法检测P53外显子4-8的突变。对CD117和p53水平或P53突变与临床参数之间的关联进行统计学评估。TNBC患者中CD117或MKI67阳性率、CD117/P53错义突变、P53错义突变或复发率显著高于非TNBC患者。在TNBC组织中，CD117的存在与P53错义突变（P=0.031）、血管侵袭、复发和MKI67相关。CD117/P53错义突变也与血管侵袭、复发和MKI67相关。单因素分析显示，MKI67、血管侵袭、CD117、CD117/P53错义突变和P53错义突变与TNBC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袭和CD117/P53错义突变是TNBC患者的独立预后因素。总之，CD117/P53错义突变与TNBC中的MKI67、血管侵袭和肿瘤复发相关。原发性肿瘤中同时存在CD117和P53错义突变是TNBC患者生存的独立预后因素。
