title: The precrystalline cytoplasmic granules of alveolar soft part sarcoma contain monocarboxylate transporter 1 and CD147.
abstract: Alveolar soft part sarcoma (ASPS) is an unusual tumor of young adults with the characteristic presence on ultrastructural analysis of rhomboid or rectangular cytoplasmic crystals. These membrane-bound crystals are known to form within specific PAS-diastase-resistant electron-dense cytoplasmic granules. The composition of these crystals and the dense granules from which they are derived has remained elusive. After the detection of strong discrete granular cytoplasmic immunoreactivity in ASPS for monocarboxylate transporter 1 (MCT1) in the course of a broad immunohistochemical characterization of an MCT1 antibody, we studied the expression of MCT1 and its interacting partner, CD147, in a panel of 10 ASPS cases using appropriate antibodies. MCT1 is one of a family of widely expressed proton-linked transporters for monocarboxylates such as lactate and pyruvate. In all normal and neoplastic tissues studied to date, MCT1 immunoreactivity is limited to the cell surface. We find that the periodic acid-Schiff-diastase-resistant cytoplasmic granules of ASPS are strongly immunoreactive for MCT1 and CD147. Specifically, intense cytoplasmic granular positivity for MCT1 and CD147 was found in 7 of 10 and 8 of 10 ASPSs, respectively. Ultrastructural immunohistochemistry with immunogold labeling confirmed that the MCT1 immunoreactivity localized to the cytoplasmic electron-dense granules in ASPS. Western blot analysis of several ASPS cases confirmed that the protein reactive with the MCT1 antibody and that reactive with the CD147 antibody both migrated at the size expected for MCT1 and CD147, respectively. Thus, ASPS cells seem to accumulate MCT1-CD147 complexes in the specific cytoplasmic granules known to undergo crystallization. The possible basis for the overproduction or impaired surface localization of these proteins in ASPS remains unclear.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. ladanyi@mskcc.org
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: Marija
authors.initials: M
authors.lastname: Drobnjak
authors.forename: Ann
authors.initials: A
authors.lastname: Baren
authors.forename: Man Yee
authors.initials: MY
authors.lastname: Lui
authors.forename: David W
authors.initials: DW
authors.lastname: Golde
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
mesh_terms: D000328:Adult; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D015153:Blotting, Western; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism* / Q000648:ultrastructure; D011650:Pulmonary Alveoli; D027981:Symporters / Q000378:metabolism* / Q000648:ultrastructure; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D008562:Membrane Glycoproteins; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat