title: Metabolic phenotypes in primary unknown metastatic carcinoma.
abstract: BACKGROUND
  The purpose of this study is to evaluate expression of metabolism-related proteins in primary unknown metastatic carcinoma (PUMC) and associated implications for treatment.
  
  
  METHODS
  A tissue microarray containing 77 cases of PUMC was constructed and immunohistochemical staining was used to evaluate expression of the following proteins: Glycolysis-related: Glut-1, carbonic anhydrase (CA) IX, and monocarboxylate transporter (MCT) 4; Glutaminolysis-related: glutaminase1 (GLS1), glutamate dehydrogenase (GDH), and amino acid transporter-2 (ASCT2); and Mitochondrial-related: ATP synthase, succinate dehydrogenase (SDH)A, and SDHB. The association between immunohistochemical staining results and clinicopathologic parameters was evaluated.
  
  
  RESULTS
  The expression of metabolism-related proteins was different depending on the histologic subtype. Compared to other subtypes, squamous cell carcinomas (SQ) expressed more Glut-1 (p = 0.028), while adenocarcinomas (AD) expressed more SDHB in the stroma (p = 0.025). The expression of metabolism-related proteins was also different depending on the clinical subtypes. Glut-1 was expressed most in the nodal type and the least in carcinomatosis type, when compared to other subtypes (p = 0.021). The metabolic phenotypes also showed other trends: when the stroma showed no glutaminolysis, the tumor mostly invaded lymph node, bone, and brain, while the tumor invaded regions other than lymph node, bone, and brain when the stroma showed glutaminolysis (p = 0.003). When the stroma showed the mitochondrial metabolic type, the histologic subtype was mainly AD, but the non-mitochondrial type was associated more with SQ (P = 0.049).
  
  
  CONCLUSIONS
  For PUMC, the expression of metabolism-related proteins, such as Glut-1 and SDHB, differs in the tumor or stroma depending on the clinical and histologic tumor subtype.
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Do Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Woo Hee
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, South Korea. kjs1976@yuhs.ac.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D009382:Neoplasms, Unknown Primary / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D051272:Glucose Transporter Type 1; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; C495677:SLC2A1 protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase