title: Multicompartment metabolism in papillary thyroid cancer.
abstract: In many cancers, varying regions within the tumor are often phenotypically heterogeneous, including their metabolic phenotype. Further, tumor regions can be metabolically compartmentalized, with metabolites transferred between compartments. When present, this metabolic coupling can promote aggressive behavior. Tumor metabolism in papillary thyroid cancer (PTC) is poorly characterized.
  
  
  
  Immunohistochemical staining of tissue samples.
  
  
  
  Papillary thyroid cancer specimens from 46 patients with (n = 19) and without advanced disease (n = 27) were compared to noncancerous thyroid tissue (NCT) and benign thyroid specimens (n = 6 follicular adenoma [FA] and n = 5 nodular goiter [NG]). Advanced disease was defined as the presence of lateral neck lymphadenopathy. Immunohistochemistry was performed for translocase of outer mitochondrial membrane 20 (TOMM20), a marker of oxidative phosphorylation, and monocarboxylate transporter 4 (MCT4), a marker of glycolysis.
  
  
  
  Papillary thyroid cancer and FA thyrocytes had high staining for TOMM20 compared to NCT and nodular goiter (NG) (P < 0.01). High MCT4 staining in fibroblasts was more common in PTC with advanced disease than in any other tissue type studied (P < 0.01). High MCT4 staining was found in all 19 cases of PTC with advanced disease, in 11 of 19 samples with low-stage disease, in one of five samples of FA, in one of 34 NCT, and in 0 of six NG samples. Low fibroblast MCT4 staining in PTC correlated with the absence of clinical adenopathy (P = 0.028); the absence of extrathyroidal extension (P = 0.004); low American Thyroid Association risk (P = 0.001); low AGES (age, grade, extent, size) score (P = 0.004); and low age, metastasis, extent of disease, size risk (P = 0.002).
  
  
  
  This study suggests that multiple metabolic compartments exist in PTC, and low fibroblast MCT4 may be a biomarker of indolent disease.
  
  
  
  N/A. Laryngoscope, 126:2410-2418, 2016.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Curry
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cotzia
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA.
authors.forename: John
authors.initials: J
authors.lastname: Sprandio
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Adam
authors.initials: A
authors.lastname: Luginbuhl
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: David M
authors.initials: DM
authors.lastname: Cognetti
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Mehri
authors.initials: M
authors.lastname: Mollaee
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Marina
authors.initials: M
authors.lastname: Domingo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Edmund A
authors.initials: EA
authors.lastname: Pribitkin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: William M
authors.initials: WM
authors.lastname: Keane
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Zhan
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Birbe
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Madalina
authors.initials: M
authors.lastname: Tuluc
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Martinez-Outschoorn
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000072645:Cancer-Associated Fibroblasts / Q000502:physiology*; D002277:Carcinoma / Q000378:metabolism*; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D002451:Cell Compartmentation / Q000502:physiology*; D005260:Female; D006044:Goiter, Nodular / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D027501:Monocarboxylic Acid Transporters / Q000032:analysis; D009124:Muscle Proteins / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D011956:Receptors, Cell Surface; C406962:SLC16A4 protein, human; C084008:TOMM20 protein, human
keywords: cancer; coupling; metabolism; papillary; thyroid