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Lung Cancer. 2019 Apr;130:135-142. doi: 10.1016/j.lungcan.2019.02.015. Epub 2019 Feb 18.

A study of ALK-positive pulmonary squamous-cell carcinoma: From diagnostic methodologies to clinical efficacy.

Author information

1
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
2
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
3
Oncology Business Division, Beijing Novogene Bioinformatics Technology Co., Ltd, Beijing, People's Republic of China.
4
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic OncologyⅡ, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
5
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic OncologyⅠ, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
6
University Health Network/Princess Margaret Cancer Centre and University of Toronto, Toronto, Canada.
7
Pathology Department, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, People's Republic of China. Electronic address: shihuaiyin@sina.com.
8
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China. Electronic address: lindm3@163.com.

Abstract

BACKGROUND:

High concordance has been observed between Ventana D5F3 ALK immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) in lung adenocarcinoma (LADC). However, whether a similar conclusion can be applied to lung squamous-cell carcinoma (LSCC) has remained unclear. We therefore evaluated the ALK (anaplastic lymphoma kinase) status and the therapeutic effect of an ALK tyrosine kinase inhibitor (TKI) in IHC- or FISH-positive LSCC.

MATERIALS AND METHODS:

A total of 2403 LSCC patients from three institutions were screened for ALK aberration by IHC. All IHC-positive cases were subjected to FISH (with an approximately equal number of negative cases as a control group) and next-generation sequencing (NGS). Clinical efficacy was evaluated for the patients who received TKI therapy.

RESULTS:

In 2403 cases of LSCC, 37 cases were identified as ALK-positive by IHC. After quality control, 28 cases were succeeded by FISH (six with insufficient tissue, three with lack of signals) and 13 by NGS (24 failed due to insufficient samples or poor DNA quality); the percentage of non-diagnostic tests was 24.3% (9/37) and 64.9% (24/37), respectively. Four cases (4/2394, 0.17%) analyzed by FISH were determined as ALK-positive. For the control group (40 ALK IHC), FISH demonstrated no samples with ALK gene fusion. The concordance between ALK IHC- and ALK FISH-positive results was 14.3% (4/28). In the 13 cases studied by NGS, two cases showed ALK-EML4 fusion (consistent with two FISH-positive results), and two cases were interpreted as harboring an ALK-association gene mutation. Among four patients (two FISH-positive and two IHC-positive only cases) receiving TKI therapy, two patients had stable disease and the other two had progressive disease.

CONCLUSIONS:

The positive concordance rate of ALK IHC and FISH in LSCC is far less than that reported for LADC. Therefore, ALK IHC detection in LSCC cannot be used as a diagnostic method for ALK rearrangement.

KEYWORDS:

ALK gene rearrangement; Lung squamous-cell carcinoma; Ventana D5F3 ALK immunohistochemistry

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