title: Prognostic significance of lactate/proton symporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  To investigate the prognostic significance of lactate/proton monocarboxylate transporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder (UCB).
  
  
  METHODS
  We examined the expressions of MCT1, MCT4, and CD147 proteins in a total of 360 cases of UCB by immunohistochemistry. The immunohistochemical expressions were quantified using an ImageJ-based analysis program.
  
  
  RESULTS
  MCT1, MCT4, and CD147 expressions were increased in 130 (36.1%), 168 (46.7%), and 228 (63.3%) UCB cases, respectively. Most tumor cells showed diffuse membranous staining, whereas normal urothelial cells showed negative or weak staining. High levels of MCT1 expression correlated with high World Health Organization grade (P<.001), advanced tumor node metastasis (TNM) stage (P<.001), nonpapillary growth type (P<.001), and lymphatic tumor invasion (P=.010), whereas high levels of MCT4 expression did not significantly correlate with any of these variables. High CD147 expression was associated with high World Health Organization grade (P<.001), advanced tumor node metastatis stage (P<.001), and nonpapillary growth type (P=.003). Univariate analyses revealed that high MCT1 (P<.001) and CD147 (P=.029) expressions were associated with poor overall survival and that high MCT4 expression was correlated with poor recurrence-free survival (P=.036). Multivariate analyses revealed that high MCT1 and MCT4 expressions were independent prognostic factors for poor overall survival and poor recurrence-free survival, respectively, in UCB patients.
  
  
  CONCLUSIONS
  Our results indicate that increased MCT1, MCT4, and CD147 expressions have prognostic implications in UCB and suggest their roles in urothelial cancer metabolism.
authors.affiliation: Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Younghye
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Ju-Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea. Electronic address: apysk@korea.ac.kr.
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051926:Basigin / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007773:Lactates / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis*; D009124:Muscle Proteins / Q000096:biosynthesis*; D011379:Prognosis; D016019:Survival Analysis; D027981:Symporters / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D055815:Young Adult; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D051926:Basigin; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human; C406962:SLC16A4 protein, human