Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Br J Surg. 2013 Mar;100(4):490-6. doi: 10.1002/bjs.9021. Epub 2013 Jan 14.
As patients with basal-like breast cancer (BLBC) have a poor prognosis and there is no specifically tailored therapy, molecular biological characterization of BLBC is necessary. c-Kit is a transmembrane receptor tyrosine kinase known to play important roles in various solid cancers. This study classified BLBCs from patients with breast carcinoma, and addressed the significance of c-Kit expression in these tumours.
Primary breast tumours were stained with antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER) 2, epidermal growth factor receptor (EGFR), cytokeratin 5/6 and c-Kit. The association between c-Kit, BLBC and survival was analysed.
A total of 667 patients with breast cancer were followed up for a median of 39 (range 6-72) months. Some 190 tumours (28·5 per cent) were classified as triple-negative for breast cancer (negative for oestrogen receptor, progesterone receptor and HER2) and 149 (78·4 per cent) had characteristics of BLBC (positive for cytokeratin 5/6 and/or EGFR). c-Kit expression was detected in 111 (16·6 per cent) of 667 tumours. c-Kit-positive tumours were more commonly found among patients with BLBC (42 of 149, 28·2 per cent; P < 0·001) and in patients with nodal metastasis (47 of 216, 21·8 per cent; P = 0·014) than in those without. In patients with BLBC, the prognosis was significantly worse in those with c-Kit expression (P < 0·001). Multivariable logistic regression analysis revealed c-Kit as an independent negative prognostic factor for cancer-specific survival in patients with BLBC (hazard ratio 2·29, 95 per cent confidence interval 1·11 to 4·72).
c-Kit might be a prognostic marker and possible molecular target for therapy in patients with BLBC.
基底样乳腺癌（BLBC）患者预后较差，且尚无针对性治疗方法，因此有必要对其进行分子生物学特征分析。c-Kit 是一种已知在多种实体瘤中发挥重要作用的跨膜受体酪氨酸激酶。本研究对乳腺癌患者的 BLBC 进行分类，并探讨 c-Kit 表达在这些肿瘤中的意义。
对原发性乳腺癌组织标本进行雌激素受体、孕激素受体、人表皮生长因子受体 2（HER2）、表皮生长因子受体（EGFR）、细胞角蛋白 5/6 和 c-Kit 免疫组织化学染色。分析 c-Kit 与 BLBC 及生存的相关性。
共 667 例乳腺癌患者随访中位时间为 39 个月（范围 6-72 个月）。190 例（28.5%）肿瘤被归类为三阴性乳腺癌（雌激素受体、孕激素受体和 HER2 均阴性），149 例（78.4%）具有 BLBC 特征（细胞角蛋白 5/6 和/或 EGFR 阳性）。在 667 例肿瘤中，检测到 111 例（16.6%）c-Kit 阳性。在 BLBC 患者中（42/149，28.2%；P<0.001）和淋巴结转移患者中（47/216，21.8%；P=0.014），c-Kit 阳性肿瘤更常见。在 BLBC 患者中，c-Kit 表达与预后显著相关（P<0.001）。多变量 logistic 回归分析显示，c-Kit 是 BLBC 患者癌症特异性生存的独立预后不良因素（危险比 2.29，95%置信区间 1.11-4.72）。
c-Kit 可能是 BLBC 患者的预后标志物和潜在治疗靶点。
