The first and second authors contributed equally and are joint first authors.
Molecular characterization of kidney cancer†
Association of hyaluronic acid family with histological subtypes and metastasis
Article first published online: 1 SEP 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 9, pages 2394–2402, 1 May 2012
How to Cite
Chi, A., Shirodkar, S. P., Escudero, D. O., Ekwenna, O. O., Yates, T. J., Ayyathurai, R., Garcia-Roig, M., Gahan, J. C., Manoharan, M., Bird, V. G. and Lokeshwar, V. B. (2012), Molecular characterization of kidney cancer. Cancer, 118: 2394–2402. doi: 10.1002/cncr.26520
We thank Drs. John Shields and Mohamed Aziz, University of Miami Miller School of Medicine, for their help in specimen collection.
- Issue published online: 20 APR 2012
- Article first published online: 1 SEP 2011
- Manuscript Accepted: 15 JUL 2011
- Manuscript Revised: 12 JUL 2011
- Manuscript Received: 2 JUN 2011
- prognostic markers;
- HA synthase;
- HA receptors;
- renal cell carcinoma;
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.
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.
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.
CD44s and RHAMM levels distinguish between oncocytoma and RCC subtypes regardless of tumor size and are potential predictors of RCC metastasis. Cancer 2012. © 2011 American Cancer Society.