Identification of anaplastic lymphoma kinase fusions in renal cancer

Large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method

Authors

  • Emiko Sugawara MD,

    1. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
    2. Department of Comprehensive Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
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  • Yuki Togashi MS,

    1. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
    2. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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  • Naoto Kuroda MD,

    1. Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi City, Kochi, Japan
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  • Seiji Sakata MD, PhD,

    1. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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  • Satoko Hatano BS,

    1. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
    2. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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  • Reimi Asaka BS,

    1. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
    2. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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  • Takeshi Yuasa MD, PhD,

    1. Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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  • Junji Yonese MD, PhD,

    1. Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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  • Masanobu Kitagawa MD, PhD,

    1. Department of Comprehensive Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
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  • Hiroyuki Mano MD, PhD,

    1. Division of Functional Genomics, Jichi Medical University, Tochigi, Japan
    2. Department of Medical Genomics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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  • Yuichi Ishikawa MD, PhD,

    1. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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  • Kengo Takeuchi MD, PhD

    Corresponding author
    1. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
    2. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
    • Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo 135-8550, Japan

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    • Fax: (011) 81 3-3570-0230


Abstract

BACKGROUND:

Several promising molecular-targeted drugs are used for advanced renal cancers. However, complete remission is rarely achieved, because none of the drugs targets a key molecule that is specific to the cancer, or is associated with “oncogene addiction” (dependence on one or a few oncogenes for cell survival) of renal cancer. Recently, an anaplastic lymphoma kinase (ALK) fusion, vinculin-ALK, has been reported in pediatric renal cell carcinoma (RCC) cases who have a history of sickle cell trait. In this context, ALK inhibitor therapy would constitute a therapeutic advance, as has previously been demonstrated with lung cancer, inflammatory myofibroblastic tumors, and anaplastic large cell lymphomas.

METHODS:

Anti-ALK immunohistochemistry was used to screen 355 tumor tissues, using the intercalated antibody-enhanced polymer (iAEP) method. The cohort consisted of 255 clear cell RCCs, 32 papillary RCCs, 34 chromophobe RCCs, 6 collecting duct carcinomas, 10 unclassified RCCs, 6 sarcomatoid RCCs, and 12 other tumors.

RESULTS:

Two patients (36- and 53-year-old females) were positive for ALK as determined by iAEP immunohistochemistry. Using 5′- rapid amplification of complementary DNA ends, we detected TPM3-ALK and EML4-ALK in these tumors. The results of this study were confirmed by fluorescence in situ hybridization assays. The 2 ALK-positive RCCs were unclassified (mixed features of papillary, mucinous cribriform, and solid patterns with rhabdoid cells) and papillary subtype. They comprised 2.3% of non–clear cell RCCs (2 of 88) and 3.7% of non–clear cell and nonchromophobe RCCs (2 of 54).

CONCLUSIONS:

The results of this study indicate that ALK fusions also exist in adult RCC cases without uncommon backgrounds. These findings confirm the potential of ALK inhibitor therapy for selected cases of RCC. Cancer 2012. © 2012 American Cancer Society.

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