title: Anaplastic lymphoma kinase protein expression, genetic abnormalities, and phosphorylation in soft tissue tumors: Phosphorylation is associated with recurrent metastasis.
abstract: Gene and protein abnormalities of anaplastic lymphoma kinase (ALK) play an important role in the pathogenesis of various cancers and serve as important therapeutic targets. We investigated ALK protein expression, phosphorylation, and genetic aberrations using fluorescence in situ hybridization (FISH) in 81 soft tissue tumor samples: inflammatory myofibroblastic tumor, n=1; alveolar soft part sarcoma, n=2; leiomyosarcoma, n=10; well-differentiated liposarcoma, n=7; pleomorphic liposarcoma, n=2; extraskeletal osteosarcoma, n=1; epithelioid sarcoma, n=1; synovial sarcoma, n=4; malignant peripheral nerve sheath tumor, n=4; undifferentiated pleomorphic sarcoma, n=19; rhabdomyosarcoma, n=6; myxofibrosarcoma, n=8; myxoid liposarcoma, n=11; fibrosarcoma, n=4; and desmoid-type fibromatosis, n=1. ALK protein expression, gene signal gain (without translocation), and phosphorylation were observed in 33/81 (40.7%), 55/81 (67.9%), and 30/81 (37.0%) tumor samples, respectively. ALK protein expression was statistically associated with phosphorylation, but not with gene signal gain. ALK phosphorylation-positive cases showed a statistically worse metastasis-free survival compared with phosphorylation-negative cases (P=0.0215). Particularly, metastasis of myxoid liposarcoma was associated with ALK phosphorylation (P=0.0019), but not with ALK protein expression or gene signal gain. However, the prognosis had no association with ALK protein expression, gene signal gain, or phosphorylation. ALK protein expression and phosphorylation play an important role in tumor biology and provide potential therapeutic targets for soft tissue tumors. Future research should focus on the oncogenic role and the efficacy of potential inhibitors of ALK.
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Yukinao
authors: Y
authors: Ishibashi
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Hiroaki
authors: H
authors: Miyoshi
authors: Department of Orthopedic Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Koji
authors: K
authors: Hiraoka
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Fumiko
authors: F
authors: Arakawa
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Toshiaki
authors: T
authors: Haraguchi
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Shinji
authors: S
authors: Nakashima
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Toshihiro
authors: T
authors: Hashiguchi
authors: Department of Orthopedic Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Takanori
authors: T
authors: Shoda
authors: Department of Orthopedic Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Tetsuya
authors: T
authors: Hamada
authors: Department of Orthopedic Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Takahiro
authors: T
authors: Okawa
authors: Department of Orthopedic Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Fujio
authors: F
authors: Higuchi
authors: Department of Orthopedic Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Naoto
authors: N
authors: Shiba
authors: Department of Orthopedic Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Kensei
authors: K
authors: Nagata
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan.
authors: Koichi
authors: K
authors: Ohshima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases