ALK Expression in Small Cell Lung Cancer

Abstract

Introduction

ALK immunohistochemistry has shifted from a screening tool to a sole determinant for ALK‐targeted therapy. Recent articles have referred to SCLC transformation as a resistance mechanism after ALK inhibitor treatments, but few reports have addressed ALK expression in treatment‐naïve SCLC in a comprehensive manner.

Methods

We examined ALK expression in a consecutive series of SCLC tumors, and the expression mechanism was analyzed 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.

Results

Immunohistochemical results revealed that ALK was positive in 16 of 142 (11.3%) SCLCs. The expression was focal and less intense, which is in contrast to strong and uniform expression in adenocarcinoma with ALK rearrangement. Two combined SCLCs 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. An SCLC cell line, SKLC2, which expressed ALK without known genetic alterations, was not inhibited with a practical concentration of crizotinib.

Conclusions

ALK IHC for treatment‐naïve SCLCs 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.

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