EGFR expression and gene copy number in triple-negative breast carcinoma
EGFR expression and gene copy number in triple-negative breast carcinoma
复制标题
DOI：
10.1016/j.cancergencyto.2010.07.118
复制
发表时间：
2010-12-01
影响因子：
--
通讯作者：
Guler, Gulnur
中科院分区：
文献类型：
--
作者：
Gumuskaya, Berrak;Alper, Murat;Guler, Gulnur
大多数基底细胞样乳腺癌是雌激素受体阴性、孕激素受体阴性和cerb-B2/HER-2/neu阴性的，即所谓的三阴性乳腺癌，具有高表皮生长因子受体（EGFR）表达，这使得EGFR成为治疗的靶点。我们用两种不同的克隆（EGFR.31G7和EGFR.25）通过免疫组织化学（IHC）评估了62例三阴性乳腺癌中EGFR的表达，并用基因座特异性标识符EGFR/CEP 7双探针通过荧光原位杂交（FISH）评估了基因拷贝数。任何完全或不完全的膜和/或细胞质表达均视为IHC阳性。显示基因扩增（EGFR基因与7号染色体的比率>= 2或15拷贝/细胞，>= 10%的细胞）和高度多体性（>= 4拷贝，>= 40%的细胞）的病例被认为是FISH阳性。我们在62例病例中的38例（61.4%）中检测到EGFR. 31 G7阳性，其中12例（19.4%）为胞浆染色，14例（22.6%）为不完全膜染色，12例（19.4%）为完全膜染色。在38/49例（77.6%）EGFR. 25阳性病例中，7/49例（14.3%）表现为胞浆染色，10/49例（20.4%）表现为不完全膜染色，21/49例（42.9%）表现为完全膜染色模式。62例FISH阳性病例中有10例（16.1%）被鉴定; 62例中有1例（1.6%）显示扩增，其余显示高度多体性。两种EGFR克隆均发现所有FISH阳性病例均为IHC阳性（P = 0.01）。扩增的情况下，显示强烈的完全膜染色与两个克隆。在高多体病例中，检测到EGFR. 31 G7的9例中的4例（44.4%）不完全膜表达、9例中的4例（44.4%）完全膜表达和9例中的1例（11.1%）胞质表达，以及EGFR. 25的8例中的6例（75%）完全膜表达和6例中的2例（25%）胞质表达。在这里，我们报告了膜EGFR表达与基因拷贝数增加相关（EGFR. 31 G7的P = 0. 035，EGFR. 25克隆的P = 0. 026）。由于在其他系统肿瘤中预测抗EGFR治疗反应的标志物（如EGFR突变和扩增）在乳腺癌中似乎是罕见事件，因此EGFR的膜染色模式可能是决定患者是否适合抗EGFR治疗的最佳方法。(C)2010年爱思唯尔公司All rights reserved.
Most basal-like breast carcinomas are estrogen receptor negative, progesterone receptor negative, and cerb-B2/HER-2/neu negative-the so-called triple-negative breast carcinomas-with high epidermal growth factor receptor (EGFR) expression, which makes EGFR a target of treatment. We evaluated EGFR expression by immunohistochemistry (IHC) with two different clones (EGFR.31G7 and EGFR.25) and gene copy number by fluorescence in situ hybridization (FISH) with Locus specific identifier EGFR/CEP 7 dual probe in 62 triple-negative breast carcinomas. Any complete or incomplete membranous and/or cytoplasmic expression was regarded as IHC positive. Cases showing gene amplification (a ratio of EGFR gene to chromosome 7 of >= 2 or 15 copies per cell in >= 10% of cells) and high polysomy (>= 4 copies in >= 40% of cells) were considered FISH positive. We detected EGFR.31G7 positivity in 38 of 62 cases (61.4%), which was composed of 12 of 62 (19.4%) cytoplasmic, 14 of 62 (22.6%) incomplete membranous, and 12 of 62 (19.4%) complete membranous staining. Among 38 of 49 (77.6%) EGFR.25-positive cases, 7 of 49 (14.3%) exhibited cytoplasmic, 10 of 49 (20.4%) exhibited incomplete membranous, and 21 of 49 (42.9%) exhibited complete membranous staining pattern. Ten of 62 (16.1%) FISH-positive cases were identified; 1 of 62 (1.6%) showed amplification, and the rest showed high polysomy. All FISH-positive cases were also found to be IHC positive (P = 0.01) by both EGFR clones. The amplified case displayed strong complete membranous staining with both clones. Among the high polysomic cases; 4 of 9 (44.4%) incomplete membranous, 4 of 9 (44.4%) complete membranous and 1 of 9 (11.1%) cytoplasmic expression of EGFR.31G7, and 6 of 8 (75%) complete membranous and 2 of 6 (25%) cytoplasmic expression of EGFR.25 were detected. Here, we report that membranous EGFR expression is associated with increased gene copy number (P = 0.035 for EGFR.31G7 and P = 0.026 for EGFR.25 clone). Because the markers to predict anti-EGFR treatment response in other system tumors such as EGFR mutation and amplification seem to be rare events in breast cancer, membranous staining pattern of EGFR might be the best way to decide the patient eligibility for anti-EGFR therapy. (C) 2010 Elsevier Inc. All rights reserved.