Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
J Thorac Oncol. 2011 Aug;6(8):1407-12. doi: 10.1097/JTO.0b013e31821d41af.
The clinical significance of epidermal growth factor receptor (EGFR) mutant allele specific imbalance (MASI) in lung adenocarcinomas is unknown.
EGFR MASI was characterized by sequencing electropherograms (SEs) and EGFR fluorescence in situ hybridization (FISH) in 96 prospectively tested lung adenocarcinoma patients with a median follow-up of 20 months (all cases were EGFR mutation-positive).
In 25 cases, the mutant allele (MA) peak was higher than the wild-type allele (WA) peak, indicating the presence of EGFR MASI (25/96, 26%). The adenocarcinomas with EGFR MASI had a 4.4-fold higher average EGFR/Chromosome Enumeration Probe 7 ratio than carcinomas without MASI (7.9 ± 3.8 versus 1.8 ± 0.6, p = 0.01). A high degree of correlation between the MA/WA ratio (SE) and the EGFR/CEP7 ratio (FISH) (ρ = 0.757, p = 0.003) validated the quantitative nature of SE. Amplification was the most common mechanism of EGFR MASI (13/21, 62%). EGFR MASI was more commonly associated with exon 19 mutations than with exon 21 mutations (19/53, 36%, versus 6/43, 14%, p = 0.015, odds ratio [OR] = 3.4) and in patients younger than 65 years (17/46, 37%, versus 8/50, 16%, p = 0.019, OR = 3.1). Patients with EGFR MASI presented with stage IV disease more frequently (p = 0.01, OR = 3.5) and had a poorer disease-specific survival rate (p = 0.021, 54% versus 83% at 31 months).
EGFR MASI in lung adenocarcinomas can be assessed based on SE and can be used to identify younger patients with more aggressive disease.
表皮生长因子受体（EGFR）突变等位基因特异性不平衡（MASI）在肺腺癌中的临床意义尚不清楚。
对 96 例经前瞻性检测的肺腺癌患者（中位随访时间为 20 个月，所有病例均为 EGFR 突变阳性）的 EGFR MASI 进行测序电泳图（SE）和 EGFR 荧光原位杂交（FISH）特征分析。
在 25 例中，突变等位基因（MA）峰高于野生型等位基因（WA）峰，表明存在 EGFR MASI（25/96，26%）。与无 MASI 的癌相比，有 MASI 的腺癌的 EGFR/染色体计数探针 7 比值的平均倍数更高（7.9±3.8 与 1.8±0.6，p=0.01）。MA/WA 比值（SE）与 EGFR/CEP7 比值（FISH）高度相关（ρ=0.757，p=0.003），验证了 SE 的定量性质。扩增是 EGFR MASI 的最常见机制（13/21，62%）。与外显子 21 突变相比，EGFR MASI 更常见于外显子 19 突变（19/53，36%，与 6/43，14%，p=0.015，优势比[OR]=3.4），且更常见于 65 岁以下患者（17/46，37%，与 8/50，16%，p=0.019，OR=3.1）。EGFR MASI 患者更常出现 IV 期疾病（p=0.01，OR=3.5），且疾病特异性生存率更差（p=0.021，31 个月时 54%与 83%）。
肺腺癌中的 EGFR MASI 可以通过 SE 进行评估，并可用于识别更具侵袭性疾病的年轻患者。
