title: Hepatic angiomyolipomas may overexpress TFE3, but have no relevant genetic alterations.
abstract: The fusion or amplification of TFE3 has been identified as one of the molecular events underlying tumorigenesis in perivascular epithelioid cell tumors (PEComas). TFE3 rearrangements in PEComas are related to the morphological features of the epithelioid appearance and weaker expression of immunohistochemical muscular markers. This study aimed to clarify whether these genetic alterations are involved in hepatic angiomyolipomas (AMLs), which are a member of the PEComa tumor family. We examined 28 liver specimens (15 biopsies and 13 surgical specimens) of hepatic AMLs obtained from 26 patients. Renal AMLs (n=20), extrahepatorenal PEComas (n=3), lymphangiomyomatosis (n=8), and hepatocellular carcinomas (n=40) were used as a control. A histologic comparison between hepatic and renal AMLs revealed that the epithelioid appearance was more common in hepatic tumors (38% versus 0%, P=.006). In immunohistochemistry, the expression of HMB45 and Melan-A appeared to be more widespread in hepatic AMLs than in renal AMLs, whereas smooth muscle actin and desmin were less broadly expressed in hepatic tumors (all P<.001). TFE3 also appeared to be overexpressed in 6 (21%) of 26 hepatic AMLs and 3 (100%) of 3 PEComas, but in none of the renal AMLs. In fluorescence in situ hybridization, although all PEComas harbored a TFE3 rearrangement or amplification, no genetic alterations were found in any hepatic AMLs. In conclusion, although hepatic AMLs and TFE3-rearranged PEComas share pathological features such as the epithelioid appearance and immunoreactivity to TFE3, TFE3 alterations are less likely to be a major molecular event driving tumorigenesis in hepatic AMLs.
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: bahn_hof23@yahoo.co.jp.
authors.forename: Naoe
authors.initials: N
authors.lastname: Jimbo
authors.affiliation: Department of Diagnostic Pathology, Steel Memorial Hirohata Hospital, Himeji 671-1122, Japan. Electronic address: t_nishigami@hirohata-hp.or.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishigami
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan. Electronic address: nmasayuk@md.tsukuba.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Ultrasound Imaging Center, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: hiroko-i@hyo-med.ac.jp.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: hiros@hyo-med.ac.jp.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.affiliation: Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan. Electronic address: takumatajiri1003@yahoo.co.jp.
authors.forename: Takuma
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Pathology, Osaka City General Hospital, Osaka 534-0021, Japan. Electronic address: tak-inoue@med.osakacity-hp.or.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Pathology, Hyogo Cancer Center, Akashi 673-8558, Japan. Electronic address: thirose@hp.pref.hyogo.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: tomitoh@med.kobe-u.ac.jp.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yohzen@med.kobe-u.ac.jp.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018206:Angiolipoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; C069203:TFE3 protein, human
keywords: Angiomyolipoma; Liver; PEComa; TFE3; Tuberous sclerosis