Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas

被引:23
作者
Gow, Chien-Hung [1 ,2 ,3 ]
Hsieh, Min-Shu [4 ]
Lin, Yen-Ting [2 ,5 ]
Liu, Yi-Nan [2 ]
Shih, Jin-Yuan [2 ,5 ,6 ]
机构
[1] Far Eastern Mem Hosp, Dept Internal Med, New Taipei 22060, Taiwan
[2] Natl Taiwan Univ, Natl Taiwan Univ Hosp & Coll Med, Dept Internal Med, Taipei 10002, Taiwan
[3] Ming Chuan Univ, Dept Healthcare Informat & Management, Taoyuan 33348, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Pathol, Taipei 10002, Taiwan
[5] Natl Taiwan Univ, Grad Inst Clin Med, Taipei 10002, Taiwan
[6] Natl Taiwan Univ Hosp, Dept Med Res, Taipei 10002, Taiwan
来源
CANCERS | 2019年 / 11卷 / 06期
关键词
BRAF; immunohistochemistry; lung adenocarcinoma; overall survival; pemetrexed; MUTATION-SPECIFIC ANTIBODY; V600E MUTATION; CLINICAL CHARACTERISTICS; DRIVER MUTATIONS; CANCER; FEATURES; OUTCOMES; PROTEIN; CHEMOTHERAPY; DABRAFENIB;
D O I
10.3390/cancers11060866
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BRAF V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative diagnostic tool has not been validated. Moreover, the clinical information of patients with BRAF V600E-mutated lung ADC is limited. We retrospectively identified 31 lung ADCs diagnosed with BRAF V600E mutation by standard molecular sequencing methods and reviewed their clinical characteristics and pathological features. An anti-BRAF V600E monoclonal VE1 antibody for IHC was used to confirm the expression patterns. The series was comprised of 99 cases, 29 with BRAF V600E mutation and 70 without BRAF V600E but with other types or undetected mutations. The majority of BRAF V600E-mutated biopsied tissues were poorly differentiated and micropapillary patterns. Application of the IHC VE1 assay was highly feasible in primary/metastatic sites or effusion blocks, yielding positive findings in 28 of 29 (96.6%) BRAF V600E-mutated tumors and negative results in 69 of 70 (98.6%) tumors harboring other types or undetected mutations. Patients who received pemetrexed/platinum-based rather than mutation-targeted chemotherapy as the first-line therapy for metastatic disease showed median overall survival of 15.5 months. Our findings indicated that VE1 antibody-based IHC analysis demonstrated high sensitivity and specificity to detect BRAF V600E-mutated lung ADCs in tissues from primary or metastatic sites.
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页数:15
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