Molecular characterization of kidney cancer

Association of hyaluronic acid family with histological subtypes and metastasis

Andrew Chi, Samir P. Shirodkar, Diogo O. Escudero, Obi O. Ekwenna, Travis J. Yates, Rajinikanth Ayyathurai, Michael Garcia-Roig, Jeffrey C. Gahan, Murugesan Manoharan, Vincent G. Bird, Vinata B. Lokeshwar

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2394-2402
Number of pages9
JournalCancer
Volume118
Issue number9
DOIs
StatePublished - May 1 2012

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Kidney Neoplasms
Hyaluronic Acid
Oxyphilic Adenoma
Renal Cell Carcinoma
Neoplasm Metastasis
Neoplasms
Renal Veins
Hyaluronoglucosaminidase
Nephrectomy
Multivariate Analysis
Kidney
Sensitivity and Specificity
Polymerase Chain Reaction
Messenger RNA
Growth

Keywords

  • HA receptors
  • HA synthase
  • hyaluronidase
  • metastasis
  • oncocytoma
  • prognostic markers
  • renal cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chi, A., Shirodkar, S. P., Escudero, D. O., Ekwenna, O. O., Yates, T. J., Ayyathurai, R., ... Lokeshwar, V. B. (2012). Molecular characterization of kidney cancer: Association of hyaluronic acid family with histological subtypes and metastasis. Cancer, 118(9), 2394-2402. https://doi.org/10.1002/cncr.26520

Molecular characterization of kidney cancer : Association of hyaluronic acid family with histological subtypes and metastasis. / Chi, Andrew; Shirodkar, Samir P.; Escudero, Diogo O.; Ekwenna, Obi O.; Yates, Travis J.; Ayyathurai, Rajinikanth; Garcia-Roig, Michael; Gahan, Jeffrey C.; Manoharan, Murugesan; Bird, Vincent G.; Lokeshwar, Vinata B.

In: Cancer, Vol. 118, No. 9, 01.05.2012, p. 2394-2402.

Research output: Contribution to journalArticle

Chi, A, Shirodkar, SP, Escudero, DO, Ekwenna, OO, Yates, TJ, Ayyathurai, R, Garcia-Roig, M, Gahan, JC, Manoharan, M, Bird, VG & Lokeshwar, VB 2012, 'Molecular characterization of kidney cancer: Association of hyaluronic acid family with histological subtypes and metastasis', Cancer, vol. 118, no. 9, pp. 2394-2402. https://doi.org/10.1002/cncr.26520
Chi, Andrew ; Shirodkar, Samir P. ; Escudero, Diogo O. ; Ekwenna, Obi O. ; Yates, Travis J. ; Ayyathurai, Rajinikanth ; Garcia-Roig, Michael ; Gahan, Jeffrey C. ; Manoharan, Murugesan ; Bird, Vincent G. ; Lokeshwar, Vinata B. / Molecular characterization of kidney cancer : Association of hyaluronic acid family with histological subtypes and metastasis. In: Cancer. 2012 ; Vol. 118, No. 9. pp. 2394-2402.
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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.",
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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.

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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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