Pathology Department, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
Asian Pac J Cancer Prev. 2021 Jun 1;22(6):1935-1942. doi: 10.31557/APJCP.2021.22.6.1935.
Epidermal growth factor receptor (EGFR) gene in lung adenocarcinoma is associated with good clinical response to EGFR-tyrosine kinase therapy. The two most common EGFR gene mutations, representing 80 to 90%, are the E746-A750 deletion in exon 19 and the L858R point mutation in exon 21.
We have conducted the study to evaluate immunohistochemistry's performance in detecting the E746-A750 deletion in exon 19 of the EGFR gene in primary lung adenocarcinoma cases. This study examined 133 cases of primary lung adenocarcinoma for three years duration. The selected cases were tested for EGFR gene mutations by real-time PCR by a reference laboratory. Most cases (124) were diagnosed by tissue biopsy, though nine used cell block cytology. We performed an immunohistochemistry test on 75 cases that contained adequate diagnostic material in the paraffin block.
The test result was scored as 0 to 3+, based on the staining intensity and percentage of positive tumor cells. We evaluated the immunohistochemistry test's sensitivity and specificity compared to the EGFR gene mutations by real-time PCR. There was a significant association between gender, smoking status, and the EGFR gene mutations (P < 0.001). The overall sensitivity and specificity of the immunohistochemistry test were 40% and 100%, respectively. The positive predictive value and negative predictive values were 100% and 76.9%, each.
The immunohistochemistry has high specificity but low sensitivity in the detection of E746-A750 deletion in exon 19 of the EGFR gene. The mutation-specific antibody used in this study was unable to detect other uncommon variants of exon 19 deletions. With high specificity value, immunohistochemistry may provide an adjunct to molecular testing for detecting the most common EGFR gene mutations in cases of a low cellularity sample, financially-limited situations, or in critically ill cases where urgent targeted therapy is needed.
肺腺癌中的表皮生长因子受体（EGFR）基因与 EGFR 酪氨酸激酶治疗的良好临床反应相关。最常见的两种 EGFR 基因突变，占 80%至 90%，是外显子 19 中的 E746-A750 缺失和外显子 21 中的 L858R 点突变。
我们进行了这项研究，以评估免疫组织化学在检测原发性肺腺癌病例中 EGFR 基因外显子 19 的 E746-A750 缺失中的表现。这项研究在三年内检查了 133 例原发性肺腺癌病例。选定的病例通过参考实验室的实时 PCR 检测 EGFR 基因突变。大多数病例（124 例）通过组织活检诊断，但有 9 例使用细胞块细胞学。我们对 75 例含有足够诊断材料的石蜡块进行了免疫组织化学测试。
根据染色强度和阳性肿瘤细胞的百分比，将测试结果评为 0 至 3+。我们比较了免疫组织化学测试与实时 PCR 检测 EGFR 基因突变的敏感性和特异性。性别、吸烟状况与 EGFR 基因突变之间存在显著关联（P < 0.001）。免疫组织化学测试的总体敏感性和特异性分别为 40%和 100%。阳性预测值和阴性预测值分别为 100%和 76.9%。
在检测 EGFR 基因外显子 19 的 E746-A750 缺失方面，免疫组织化学具有高特异性但敏感性低。本研究中使用的突变特异性抗体无法检测外显子 19 缺失的其他罕见变体。免疫组织化学具有高特异性值，可为检测低细胞样本、经济受限情况或需要紧急靶向治疗的危急病例中最常见的 EGFR 基因突变提供辅助手段。
