Jain Deepali, Iqbal Sobuhi, Walia Ritika, Malik Prabhat, Cyriac Sunu, Mathur Sandeep R, Sharma Mehar C, Madan Karan, Mohan Anant, Bhalla Ashu, Pathy Sushmita, Kumar Lalit, Guleria Randeep
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.
Indian J Med Res. 2016 Mar;143(3):308-14. doi: 10.4103/0971-5916.182621.
BACKGROUND & OBJECTIVES: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC).
Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed.
Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon[20] variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases.
INTERPRETATION & CONCLUSIONS: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.
研究表明,与分子技术相比,使用表皮生长因子受体(EGFR)突变特异性抗体进行免疫组织化学(IHC)染色是一种简便且经济高效的筛查方法。本研究旨在评估使用EGFR突变特异性抗体对原发性肺腺癌(ADC)患者肺活检样本进行IHC染色的阳性率。
对206例原发性肺ADC活检样本使用针对E746 - A750缺失和L858R的EGFR突变特异性抗体。以高分辨率熔解分析(HRM)检测EGFR突变作为金标准。建立分子检测结果与IHC结果之间的一致性。评估IHC阳性频率。
206例患者中,男性129例,女性77例,平均年龄54.1岁。55例(26.6%)患者(36例男性;19例女性)E746 - A750缺失(33例)和L858R(22例)的IHC染色呈阳性。14例患者有HRM检测结果,其中64.2%的病例显示EGFR突变与E746 - 750缺失或L858R相符。HRM检测阳性的病例通过DNA测序和片段分析进一步得到证实。3例患者显示第20外显子变异。2例病例未检测到突变。E746 - 750缺失突变的基因型比L858R更常见。85.7%的病例分子突变与IHC结果一致。
在印度的这项初步研究中,使用突变特异性IHC评估EGFR的突变状态。尽管检测数量较少,但分子EGFR突变与IHC表达之间观察到良好的一致性。IHC方法是指导临床医生对肺ADC进行个体化治疗的潜在有用工具,特别是在分子分析设施不易获得的情况下,以及用于活检样本量少无法进行分子检测的情况。