免疫组织化学检测肺腺癌患者的 EGFR 突变或 ALK 重排。
Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma.
机构信息
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, CHU Nice, and Medical School, Nice Sophia University, Nice, France.
出版信息
Ann Oncol. 2012 Jul;23(7):1738-43. doi: 10.1093/annonc/mdr535. Epub 2011 Nov 18.
BACKGROUND
Immunohistochemistry has been proposed as a specific and sensitive method to identify EGFR mutations or ALK rearrangements in lung tumours.
PATIENTS AND METHODS
We assessed EGFR and KRAS by direct sequencing in 154 patients with lung adenocarcinoma. ALK rearrangements were assayed by FISH and RT-PCR. Immunohistochemistry was carried out and evaluated closely following published methods using recommended monoclonal rabbit or mouse antibodies.
RESULTS
Thirteen of 36 exon 19 EGFR-mutated tumours (36%)-including 12 of 22 with p.Glu746_Ala750del (55%)-were positive with the 6B6 antibody that was raised against p.Glu746_Ala750del. One hundred eleven of 114 EGFR exon 19 wild-type tumours (97%) were negative with 6B6. Four of 21 exon 21 EGFR-mutated tumours (19%)-including 4 of 17 with p.Leu858Arg (24%)-were positive with the 43B2 antibody that was raised against p.Leu858Arg. One hundred twenty-two of 124 (98%) EGFR exon 21 wild-type tumours were negative with 43B2. Two of four ALK rearrangements-including two of three with ELM4-ALK fusion transcripts-were identified with the 5A4 antibody. Eleven of 13 tumours without ALK rearrangement (85%) were negative with 5A4.
CONCLUSIONS
Immunohistochemistry is a specific means for identification of EGFR mutations and ALK rearrangements. It suffers, however, from poor sensitivity.
背景
免疫组织化学已被提议作为一种特定且敏感的方法来鉴定肺癌中的 EGFR 突变或 ALK 重排。
患者和方法
我们在 154 例肺腺癌患者中通过直接测序评估了 EGFR 和 KRAS。ALK 重排在 FISH 和 RT-PCR 下进行检测。免疫组织化学按照已发表的方法进行，并使用推荐的单克隆兔或鼠抗体进行了密切评估。
结果
36 个外显子 19 EGFR 突变肿瘤中有 13 个（36%）——包括 22 个 p.Glu746_Ala750del 中有 12 个（55%）——用针对 p.Glu746_Ala750del 的 6B6 抗体呈阳性。114 个外显子 19 EGFR 野生型肿瘤中有 111 个（97%）用 6B6 呈阴性。21 个外显子 21 EGFR 突变肿瘤中有 4 个（19%）——包括 17 个 p.Leu858Arg 中有 4 个（24%）——用针对 p.Leu858Arg 的 43B2 抗体呈阳性。124 个外显子 21 EGFR 野生型肿瘤中有 122 个（98%）用 43B2 呈阴性。在 2 个 ALK 重排中——包括在 3 个具有 ELM4-ALK 融合转录本的重排中——用 5A4 抗体鉴定出 2 个。在 13 个没有 ALK 重排的肿瘤中，有 11 个（85%）用 5A4 呈阴性。
结论
免疫组织化学是鉴定 EGFR 突变和 ALK 重排的一种特定手段。然而，它的敏感性较差。
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