Gumuskaya Berrak, Alper Murat, Hucumenoglu Sema, Altundag Kadri, Uner Aysegul, Guler Gulnur
2nd Pathology Department, Ankara Diskapi Yildirim Beyazit Education and Research Hospital, Irfan Bastug cad. Diskapi, Ankara 06110, Turkey.
Cancer Genet Cytogenet. 2010 Dec;203(2):222-9. doi: 10.1016/j.cancergencyto.2010.07.118.
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 po sitive. 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.
大多数基底样乳腺癌雌激素受体阴性、孕激素受体阴性且cerb - B2/HER - 2/neu阴性，即所谓的三阴性乳腺癌，其表皮生长因子受体（EGFR）表达较高，这使得EGFR成为治疗靶点。我们采用两种不同克隆（EGFR.31G7和EGFR.25）的免疫组织化学（IHC）方法评估62例三阴性乳腺癌中EGFR的表达，并采用位点特异性标识符EGFR/CEP 7双探针的荧光原位杂交（FISH）方法评估基因拷贝数。任何完整或不完整的膜性和/或细胞质表达均视为IHC阳性。显示基因扩增（EGFR基因与7号染色体的比例≥2或每细胞≥15个拷贝且≥10%的细胞中出现）和高多体性（≥40%的细胞中≥4个拷贝）的病例被视为FISH阳性。我们在62例中的38例（61.4%）检测到EGFR.31G7阳性，其中62例中的12例（19.4%）为细胞质染色、62例中的14例（22.6%）为不完整膜性染色、62例中的12例（19.4%）为完整膜性染色。在49例（77.6%）EGFR.25阳性病例中的38例中，49例中的7例（14.3%）表现为细胞质染色、49例中的10例（20.4%）表现为不完整膜性染色、49例中的21例（42.9%）表现为完整膜性染色模式。62例中的10例（16.1%）为FISH阳性病例；62例中的1例（1.6%）显示扩增，其余显示高多体性。所有FISH阳性病例通过两种EGFR克隆检测均为IHC阳性（P = 0.01）。扩增病例对两种克隆均显示强完整膜性染色。在高多体性病例中；9例中的4例（44.4%）为EGFR.31G7不完整膜性染色、9例中的4例（44.4%）为完整膜性染色和9例中的1例（11.1%）为细胞质表达，8例中的6例（75%）为EGFR.25完整膜性染色和6例中的2例（25%）为细胞质表达。在此，我们报告膜性EGFR表达与基因拷贝数增加相关（EGFR.31G7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，EGFR的膜性染色模式可能是确定患者是否适合抗EGFR治疗的最佳方法。
