Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer
Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer
复制标题
DOI：
10.1158/1078-0432.ccr-04-2064
复制
发表时间：
2005-06-01
影响因子：
11.5
通讯作者：
Foulkes, WD
中科院分区：
文献类型：
--
作者：
Arnes, JB;Brunet, JS;Foulkes, WD
目的：BRCA1 相关乳腺癌通常具有基底上皮表型，P-钙粘蛋白是一种基底标记物。我们对 P-钙粘蛋白、乳腺癌预后标志物和结果之间的关系进行了详细评估。 实验设计：本研究仅限于 1980 年至 1995 年间在德系犹太妇女中诊断的 292 例首例原发性浸润性乳腺癌。所有可用块均进行 P-钙粘蛋白染色，其中 261 例纳入最终统计分析，其中包括 27 例种系 BRCA1 突变携带者和 8 例 BRCA2 突变携带者。进行描述性分析，然后进行生存分析和泊松回归分析。结果：P-钙粘蛋白存在于 261 例乳腺癌中的 80 例 (31%) 中，并且更常见于具有基底上皮表型的肿瘤（即高级别雌激素受体和 KIP1 (p27(Kip)) 阴性肿瘤，表达细胞角蛋白 5/6、细胞周期蛋白 E、TP53 以及 BRCA1 突变和血管巢的存在 [所有 P < 0.001)]。在单变量生存模型中，P-钙粘蛋白的表达与乳腺癌死亡的相对风险 (RR) 相关，10 年随访时为 2.9（95% 置信区间，1.8-4.7；P < 0.0001），并且是淋巴结阴性和阳性乳腺癌单变量生存不良的预测因子。在多变量分析中，P-钙粘蛋白水平的影响并不独立于其他基础相关标记物。多变量相互作用模型显示，P-钙粘蛋白阳性高度预测小淋巴结阴性乳腺癌的不良预后（RR，7.1；P = 0.006）。结论：P-钙粘蛋白是基底样乳腺癌的标志物，与 BRCA1 突变的存在密切相关。它是一个不良的预后因素，特别是对于小的、淋巴结阴性的乳腺癌。
Purpose: BRCA1-related breast cancer frequently has a basal epithelial phenotype, and P-cadherin is a basal marker. We undertook a detailed evaluation of the relationship among P-cadherin, prognostic markers in breast cancer, and outcome.Experimental Design: This study was restricted to 292 cases of first primary invasive breast cancer diagnosed in Ashkenazi Jewish women between 1980 and 1995. All available blocks were stained for P-cadherin, and 261 were included in the final statistical analyses, including 27 germ line BRCA1 mutation carriers and 8 BRCA2 mutation carriers. Descriptive analyses were done followed by survival analyses and a Poisson regression analysis.Results: P-cadherin was present in 80 of the 261 breast cancers (31%) and was more frequently present in tumors that have a basal epithelial phenotype (i.e., high-grade, estrogen receptor- and KIP1 (p27(Kip)) - negative tumors, with expression of cytokeratin 5/6, cyclin E,TP53, and presence of BRCA1 mutations and vascular nests [all P < 0.001)]. In a univariate survival model, expression of P-cadherin was associated with a relative risk (RR) of death from breast cancer at a 10-year follow-up of 2.9 (95% confidence interval, 1.8-4.7; P < 0.0001) and was a predictor of poor univariate survival in both lymph node - negative and - positive breast cancers. In a multivariate analysis, the effect of P-cadherin levels was not independent of other basal-related markers. Multivariable interaction modeling showed that P-cadherin positivity was highly predictive of a poor prognosis in small, node-negative breast cancers (RR, 7.1; P = 0.006).Conclusions: P-cadherin is a marker for basal-like breast cancers and is strongly associated with the presence of a BRCA1 mutation. It is an adverse prognostic factor, particularly in small, node-negative breast cancers.