title: Use of potassium channel tetramerization domain-containing 12 as a biomarker for diagnosis and prognosis of gastrointestinal stromal tumor.
abstract: Previously, we showed that the expression of potassium channel tetramerization domain-containing 12 (KCTD12), which was discovered by a proteomics approach, is associated with high-risk behavior of gastrointestinal stromal tumors (GISTs). Here, we examined the distribution and expression of this protein by immunostaining with a commercially available polyclonal KCTD12 antibody in GISTs (n = 64) and other types of malignancy (n = 168) to clarify its diagnostic and clinical significance. Diffuse KCTD12 immunoreactivity was found in most GISTs (52 cases; 81%). KCTD12 expression was observed primarily in vascular endothelial cells, Purkinje cells of the cerebellum, and some neurons scattered throughout the cerebral cortex. KCTD12 was absent from not only the interstitial cells of Cajal but also interstitial cells of Cajal hyperplasia that was encountered incidentally in colon diverticulitis. KCTD12 immunostaining was also seen in malignant peripheral nerve sheath tumors (2/10 cases; 20%), synovial sarcomas (2/10; 20%), solitary fibrous tumor (1/8; 13%), angiosarcoma (1/7; 14%), and colon adenocarcinoma (1/24; 4%). In survival analyses, the 5-year recurrence-free survival rate of patients without KCTD12 expression was only 16.7% compared with 95.6% in those with KCTD12 expression (P < .0001). Ki-67 and KCTD12 were significant predictors of recurrence-free survival, and KCTD12 expression provided additional information about recurrence-free survival after accounting for Ki-67 status. Overall, KCTD12 expression was specific for GISTs from neoplastic and nonneoplastic adult tissues other than brain and served as a predictor of GIST recurrence. These findings suggest that KCTD12 is a useful and reliable biomarker for both the diagnosis and prognosis of GIST.
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8543, Japan. hasetada@sapmed.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.forename: Jiro
authors.initials: J
authors.lastname: Ogino
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iwaki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology; D007564:Japan / Q000453:epidemiology; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C493175:KCTD12 protein, human; D011506:Proteins