Kumari Niraj, Singh Shalini, Haloi Dhanjit, Mishra Shravan Kumar, Krishnani Narendra, Nath Alok, Neyaz Zafar
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Department of Radiotherapy, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
World J Oncol. 2019 Jun;10(3):142-150. doi: 10.14740/wjon1204. Epub 2019 Jun 29.
Epidermal growth factor receptor (EGFR) mutation is the most frequent mutation tested in lung cancer for targeted therapy in the era of personalized medicine. Knowledge about EGFR mutation is constantly expanding regarding its frequency, clinicopathological association, advancements in testing methodology and sample requirement. We investigated EGFR mutation frequency in non-small cell lung cancer (NSCLC) in North Indian patients and evaluated its diagnostic performance in cytological samples.
Molecular EGFR testing was done in 250 cases of NSCLC by both real-time polymerase chain reaction (PCR) (Therascreen) and mutation-specific EGFR immunohistochemistry (IHC). Thirty cases had both cytology samples and biopsy including 20 pleural effusions and 10 fine-needle aspirates. EGFR mutation concordance between pleural effusion and biopsy was studied.
EGFR mutation was overall 31.6% in NSCLC with 36.5% in adenocarcinoma and 15% in squamous cell carcinoma. L858R mutation accounted for 50.7% and DEL19 for 39.3% of total EGFR mutations. Complex mutations were seen in 2% of cases. Sensitivity of mutation-specific EGFR IHC was 48.3% and specificity was 92.3%. L858R showed higher sensitivity (55% vs. 33.3%) but similar specificity (93.2% vs. 91.3%) compared to DEL19. EGFR mutation was successful in 95% of pleural effusion and showed 83.3% concordance with tissue biopsy.
EGFR mutation frequency in North Indian patients was comparable to that of Asia-Pacific region and showed a similar pattern of histological distribution. EGFR mutation in squamous cell carcinomas is increasingly recognized which was 15% in our study. Mutation-specific EGFR IHC shows variable but generally low sensitivity and considering its significant pre- and post-analytical variables, it should be highly discouraged in patient management. Cytological samples may not only serve as suitable alternative but may be complementary to tissue biopsies.
在个性化医疗时代，表皮生长因子受体（EGFR）突变是肺癌靶向治疗中检测最频繁的突变。关于EGFR突变的频率、临床病理关联、检测方法的进展和样本要求等方面的知识在不断扩展。我们调查了北印度患者非小细胞肺癌（NSCLC）中的EGFR突变频率，并评估了其在细胞学样本中的诊断性能。
对250例NSCLC患者进行了分子EGFR检测，采用实时聚合酶链反应（PCR）（Therascreen）和特异性EGFR免疫组织化学（IHC）方法。30例患者同时有细胞学样本和活检样本，包括20例胸腔积液和10例细针穿刺抽吸物。研究了胸腔积液和活检样本中EGFR突变的一致性。
NSCLC中EGFR突变总体发生率为31.6%，腺癌中为36.5%，鳞状细胞癌中为15%。L858R突变占总EGFR突变的50.7%，DEL19占39.3%。2%的病例出现复杂突变。特异性EGFR IHC检测的敏感性为48.3%，特异性为92.3%。与DEL19相比，L858R显示出更高的敏感性（55%对33.3%）但特异性相似（93.2%对91.3%）。EGFR突变在95%的胸腔积液中检测成功，与组织活检的一致性为83.3%。
北印度患者的EGFR突变频率与亚太地区相当，且组织学分布模式相似。鳞状细胞癌中的EGFR突变越来越受到认可，在我们的研究中为15%。特异性EGFR IHC显示出可变但普遍较低的敏感性，考虑到其显著的分析前和分析后变量，在患者管理中应极力避免使用。细胞学样本不仅可以作为合适的替代方法，而且可能对组织活检具有补充作用。
