title: Molecular characterization of kidney cancer: association of hyaluronic acid family with histological subtypes and metastasis.
abstract: BACKGROUND
  Molecular profiling of renal cell carcinomas (RCCs) may improve the distinction between oncocytoma and malignant RCC subtypes and aid in early detection of metastasis. The hyaluronic acid (HA) family includes HA synthases (HAS1, HAS2, HAS3), hyaluronidases (HYAL-1, HYAL-2, HYAL-3, HYAL-4, PH20, HYAL-P1), and HA receptors (CD44s, CD44v, RHAMM). HA family members promote tumor growth and metastasis. The authors evaluated the expression of HA family members in kidney specimens.
  
  
  METHODS
  By using quantitative polymerase chain reaction, mRNA levels of 12 HA family members were measured in tumor specimens obtained from 86 consecutive patients undergoing nephrectomy; 80 of them also provided normal specimens. Mean and median follow-up were 15.2 ± 8.8 and 13.8 months. RCC specimens included clear cell RCC: 65; papillary: 10; chromophobe: 5; oncocytoma: 6; metastasis positive: 17.
  
  
  RESULTS
  Median HAS1, CD44s, and RHAMM transcript levels were elevated 3- to 25-fold in clear cell RCC and papillary and chromophobe tumors when compared with normal tissues. HYAL-4, CD44s, and RHAMM levels were elevated 4- to 12-fold in clear cell RCC and papillary tumors when compared with oncocytomas; only HYAL-4 levels distinguished between chromophobe and oncocytoma (P = .009). CD44s and RHAMM levels were significantly higher in tumors <4 cm (510 ± 611 and 19.6 ± 20.8, respectively) when compared with oncocytoma (46.4 ± 20 and 3.8 ± 2.5; P ≤ .006). In univariate and multivariate analyses, CD44s (P < .0001), RHAMM (P < .0001), stage, tumor size, and/or renal vein involvement were significantly associated with metastasis. The combined CD44s + RHAMM marker had 82% sensitivity and 86% specificity to predict metastasis.
  
  
  CONCLUSIONS
  CD44s and RHAMM levels distinguish between oncocytoma and RCC subtypes regardless of tumor size and are potential predictors of RCC metastasis.
authors: Department of Urology, University of Miami School of Medicine, Miami, Florida 33101, USA.
authors: Andrew
authors: A
authors: Chi
authors: Samir P
authors: SP
authors: Shirodkar
authors: Diogo O
authors: DO
authors: Escudero
authors: Obi O
authors: OO
authors: Ekwenna
authors: Travis J
authors: TJ
authors: Yates
authors: Rajinikanth
authors: R
authors: Ayyathurai
authors: Michael
authors: M
authors: Garcia-Roig
authors: Jeffrey C
authors: JC
authors: Gahan
authors: Murugesan
authors: M
authors: Manoharan
authors: Vincent G
authors: VG
authors: Bird
authors: Vinata B
authors: VB
authors: Lokeshwar
mesh_terms: D018249:Adenoma, Oxyphilic / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D006820:Hyaluronic Acid / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor; D006820:Hyaluronic Acid