Novel ALK-specific mRNA in situ hybridization assay for non-small-cell lung carcinoma

被引:6
作者
Hirai, Noriko [1 ]
Sasaki, Takaaki [1 ]
Okumura, Shunsuke [1 ]
Sado, Masatoshi [2 ]
Akiyama, Naoko [2 ]
Kitada, Masahiro [1 ,3 ]
Takei, Hidehiro [2 ]
Ohsaki, Yoshinobu [1 ]
机构
[1] Asahikawa Med Univ, Resp Ctr, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 0788510, Japan
[2] Asahikawa Med Univ, Dept Pathol, Asahikawa, Hokkaido, Japan
[3] Asahikawa Med Univ, Breast Dis Ctr, Asahikawa, Hokkaido, Japan
关键词
Anaplastic lymphoma receptor tyrosine kinase (ALK); mRNA in situ hybridization (mRNA-ISH); fluorescence in situ hybridization (FISH); immunohistochemistry (IHC); lung adenocarcinoma; MOLECULAR TESTING GUIDELINE; KINASE INHIBITORS GUIDELINE; OF-AMERICAN-PATHOLOGISTS; INTERNATIONAL-ASSOCIATION; CANCER PATIENTS; CRIZOTINIB; IMMUNOHISTOCHEMISTRY; ADENOCARCINOMAS; CLASSIFICATION; REARRANGEMENT;
D O I
10.21037/tlcr.2020.03.04
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: A recent technical advance in mRNA in situ hybridization (mRNA-ISH) assays provides simultaneous signal amplification and background suppression with a unique probe design that enables single-molecule visualization. We assessed the utility of the mRNA-ISH assay as a diagnostic tool for detecting anaplastic lymphoma receptor tyrosine kinase (ALK) mRNA in non-small-cell lung carcinoma (NSCLC). We compared the mRNA-ISH assay with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Methods: The study included 279 surgically resected lung adenocarcinomas and 44 transbronchial-biopsied (TBB) adenocarcinomas. mRNA-ISH was conducted using the RNAscope 2.0 system, which includes pre-designed probes for detecting the tyrosine kinase domain encoded in ALK mRNA. IHC was conducted on all 323 samples using ALK-specific antibodies. mRNA-ISH was performed on 279 surgical samples and 6 TBB samples. Break-apart FISH was used to examine samples that were mRNA-ISH-positive or IHC-positive. Results: ALK protein expression was detected in 11 of 279 specimens (3.9%). ALK mRNA was also detected with mRNA-ISH in ALK-positive samples, and 9 of the 11 specimens (81%) were also positive for ALK using break-apart FISH. Using the IHC results as a reference, the sensitivity and specificity of mRNA-ISH was 100%. In the TBB cohort, ALK protein expression was observed in 3 of 44 specimens (6.8%), in which ALK mRNA expression was also detected. Conclusions: The ALK mRNA-ISH data were highly correlated with the IHC data, and ALK mRNA-ISH detected ALK mRNA expression in every FISH-positive sample. We conclude that mRNA-ISH could serve as an alternative or complementary method for diagnosing ALK rearrangements in NSCLC.
引用
收藏
页码:257 / 268
页数:12
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