TY - JOUR
T1 - Molecular characterization of kidney cancer
T2 - Association of hyaluronic acid family with histological subtypes and metastasis
AU - Chi, Andrew
AU - Shirodkar, Samir P.
AU - Escudero, Diogo O.
AU - Ekwenna, Obi O.
AU - Yates, Travis J.
AU - Ayyathurai, Rajinikanth
AU - Garcia-Roig, Michael
AU - Gahan, Jeffrey C.
AU - Manoharan, Murugesan
AU - Bird, Vincent G.
AU - Lokeshwar, Vinata B.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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.
AB - 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.
KW - HA receptors
KW - HA synthase
KW - hyaluronidase
KW - metastasis
KW - oncocytoma
KW - prognostic markers
KW - renal cell carcinoma
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U2 - 10.1002/cncr.26520
DO - 10.1002/cncr.26520
M3 - Article
C2 - 21887686
AN - SCOPUS:84860225205
SN - 0008-543X
VL - 118
SP - 2394
EP - 2402
JO - Cancer
JF - Cancer
IS - 9
ER -