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Anaplastic lymphoma kinase expression in small‐cell lung cancer
Author(s) -
Kondoh Chiaki,
Horio Yoshitsugu,
Hayashi Yuko,
Ebi Hiromichi,
Hida Toyoaki,
Hasegawa Yoshinori,
Yatabe Yasushi
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13842
Subject(s) - anaplastic lymphoma kinase , lung cancer , lymphoma , anaplastic large cell lymphoma , cancer research , medicine , cancer , oncology , pathology , malignant pleural effusion
Aims Anaplastic lymphoma kinase ( ALK ) immunohistochemistry has shifted from being a screening tool to being a sole determinant for ALK ‐targeted therapy. Recent articles have referred to small‐cell lung cancer ( SCLC ) transformation as a resistance mechanism after ALK inhibitor treatments, but few reports have addressed ALK expression in treatment‐naive SCLC in a comprehensive manner. Therefore, we examined ALK expression and the mechanisms in treatment‐naive SCLC s. Methods and results We examined ALK expression in a consecutive series of SCLC tumours, and the expression mechanism was analysed regarding gene rearrangement, copy number changes, and point mutations. We also examined whether SCLC with ALK expression can be suppressed by crizotinib treatment in vitro . Immunohistochemical results revealed that ALK was expressed in 16 of 142 (11.3%) SCLC s. The expression was focal and less intense, which is in contrast to strong and uniform expression in adenocarcinoma with ALK rearrangement. Two combined SCLC s showed a positive reaction restricted to the SCLC component. None of the known genetic alterations, including rearrangement, amplification, copy number gain, or point mutations, were associated with ALK expression. A SCLC cell line, SKLC 2, which expressed ALK without known genetic alterations, was not inhibited by a practically achievable serum concentration of crizotinib. Conclusions Anaplastic lymphoma kinase immunohistochemistry for treatment‐naive SCLC s should not be used as a predictive biomarker for ALK inhibitor therapy, because the positive reactions were due to intrinsic expression of normal ALK transcript.