Parikh Rahul R, Yang Qifeng, Higgins Susan A, Haffty Bruce G
Department of Radiation Oncology, The Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):35-42. doi: 10.1016/j.ijrobp.2007.05.066. Epub 2007 Sep 12.
Basal-like carcinoma of the breast is associated with genetic instability and aggressive behavior. In this study, we evaluated the luminal cytokeratin marker CK-19 in young women with breast cancer treated with conservative surgery and radiation therapy (CS+RT).
Primary tumor specimens from a cohort of 158 young premenopausal women (range, 25-49 years) treated with CS+RT with a median follow-up of 6.25 years were constructed into a tissue microarray. The array was stained for ER, PR, HER2, CK19, and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between CK19, other co-variables, and outcome was assessed in a multivariate model.
Positive expression of ER, PR, HER-2/neu, CK19, and p53 were 33.1%, 34.5%, 10.0%, 79.5%, and 20.9%, respectively. With 20 local relapses and 38 distant metastases, the 10-year overall, breast relapse-free, and distant relapse-free survival were 79.65%, 87.29%, and 67.35%, respectively. Tumor stage and nodal status were associated with distant relapse-free and overall survival. In multivariate analysis, CK19 negativity was a predictor poor local (RR, 3.54; 95% CI, 1.87-7.65; p < 0.01) distant (RR, 1.44; 95% CI, 0.86-2.70; p = 0.17), and overall survival (RR, 1.89; 95% CI, 1.04-3.55; p = 0.03).
Lack of CK19 expression identifies a subset of patients with a significantly higher risk of local relapse. Distant relapse and overall survival rates also correlated with CK19 negativity. Further evaluation of the prognostic significance of basal and luminal cytokeratins in young women with breast cancer is warranted.
乳腺基底样癌与基因不稳定和侵袭性行为相关。在本研究中，我们评估了接受保乳手术和放射治疗（CS+RT）的年轻乳腺癌女性患者中的腔面细胞角蛋白标志物CK-19。
将158名年龄在25至49岁之间、接受CS+RT治疗且中位随访时间为6.25年的年轻绝经前女性队列的原发性肿瘤标本构建成组织芯片。该芯片进行了雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER2）、CK19和p53的染色。分子谱与临床病理因素、总生存、局部和远处无复发生存相关。在多变量模型中评估CK19、其他协变量与预后之间的关联。
ER、PR、HER-2/neu、CK19和p53的阳性表达率分别为33.1%、34.5%、10.0%、79.5%和20.9%。有20例局部复发和38例远处转移，10年总生存、无乳腺复发和无远处复发生存率分别为79.65%、87.29%和67.35%。肿瘤分期和淋巴结状态与远处无复发生存和总生存相关。在多变量分析中，CK19阴性是局部复发（风险比[RR]，3.54；95%置信区间[CI]，1.87 - 7.65；p < 0.01）、远处复发（RR，1.44；95% CI，0.86 - 2.70；p = 0.17）和总生存（RR，1.89；95% CI，1.04 - 3.55；p = 0.03）不良的预测指标。
CK19表达缺失可识别出局部复发风险显著更高的患者亚组。远处复发和总生存率也与CK19阴性相关。有必要进一步评估基底和腔面细胞角蛋白在年轻乳腺癌女性中的预后意义。
