Lakhani Sunil R, Reis-Filho Jorge S, Fulford Laura, Penault-Llorca Frederique, van der Vijver Marc, Parry Suzanne, Bishop Timothy, Benitez Javier, Rivas Carmen, Bignon Yves-Jean, Chang-Claude Jenny, Hamann Ute, Cornelisse Cees J, Devilee Peter, Beckmann Matthias W, Nestle-Krämling Carolin, Daly Peter A, Haites Neva, Varley Jenny, Lalloo Fiona, Evans Gareth, Maugard Christine, Meijers-Heijboer Hanne, Klijn Jan G M, Olah Edith, Gusterson Barry A, Pilotti Silvana, Radice Paolo, Scherneck Siegfried, Sobol Hagay, Jacquemier Jocelyne, Wagner Teresa, Peto Julian, Stratton Michael R, McGuffog Lesley, Easton Douglas F
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom.
Clin Cancer Res. 2005 Jul 15;11(14):5175-80. doi: 10.1158/1078-0432.CCR-04-2424.
To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.
Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.
All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.
The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.
研究携带种系BRCA1和BRCA2突变的患者中发生的乳腺癌表达基底标志物的比例，并开发用于识别高危患者的预测性检测方法。
作为国际乳腺癌连锁协会项目的一部分，收集了182例BRCA1突变携带者、63例BRCA2携带者和109例对照者的肿瘤组织病理学材料，对其进行细胞角蛋白14（CK14）、细胞角蛋白5/6（CK5/6）、细胞角蛋白17（CK17）、表皮生长因子受体（EGFR）和骨连接蛋白的免疫组化染色。
所有这五种基底标志物在BRCA1肿瘤中比在对照肿瘤中更常见（CK14：61%对12%；CK5/6：58%对7%；CK17：53%对10%；骨连接蛋白：43%对19%；EGFR：67%对21%；每种情况P<0.0001）。在多变量分析中，CK14、CK5/6和雌激素受体（ER）仍然是BRCA1携带者状态的显著预测因子。相比之下，BRCA2肿瘤中基底标志物的频率与对照无显著差异。
与之前可用的方法相比，联合使用细胞角蛋白染色、ER和形态学能更准确地预测BRCA1突变状态，这可能有助于选择进行BRCA1突变检测的患者。BRCA1病例中EGFR阳性率高表明，特定的抗酪氨酸激酶疗法可能对这些患者有潜在益处。
