Department of Urology, University of Miami School of Medicine, Miami, Florida 33101, USA.
Cancer. 2012 May 1;118(9):2394-402. doi: 10.1002/cncr.26520. Epub 2011 Sep 1.
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.
肾细胞癌 (RCC) 的分子谱分析可以改善嗜酸性细胞瘤和恶性 RCC 亚型之间的区分，并有助于早期发现转移。透明质酸 (HA) 家族包括 HA 合酶 (HAS1、HAS2、HAS3)、透明质酸酶 (HYAL-1、HYAL-2、HYAL-3、HYAL-4、PH20、HYAL-P1) 和 HA 受体 (CD44s、CD44v、RHAMM)。HA 家族成员促进肿瘤生长和转移。作者评估了 HA 家族成员在肾脏标本中的表达。
通过定量聚合酶链反应，测量了 86 例连续接受肾切除术的患者肿瘤标本中 12 种 HA 家族成员的 mRNA 水平；其中 80 例还提供了正常标本。平均和中位随访时间分别为 15.2 ± 8.8 和 13.8 个月。RCC 标本包括透明细胞 RCC：65 例；乳头状：10 例；嫌色细胞癌：5 例；嗜酸性细胞瘤：6 例；转移阳性：17 例。
与正常组织相比，透明细胞 RCC 和乳头状及嫌色细胞瘤的 HAS1、CD44s 和 RHAMM 转录本水平中位数升高 3-25 倍。与嗜酸性细胞瘤相比，透明细胞 RCC 和乳头状肿瘤中 HYAL-4、CD44s 和 RHAMM 水平升高 4-12 倍；只有 HYAL-4 水平可以区分嫌色细胞瘤和嗜酸性细胞瘤 (P =.009)。与嗜酸性细胞瘤相比，<4cm 肿瘤的 CD44s 和 RHAMM 水平分别升高 510 ± 611 和 19.6 ± 20.8(P ≤.006)。在单因素和多因素分析中，CD44s (P <.0001)、RHAMM (P <.0001)、分期、肿瘤大小和/或肾静脉受累与转移显著相关。联合 CD44s+RHAMM 标志物对预测转移的敏感性为 82%，特异性为 86%。
CD44s 和 RHAMM 水平可区分嗜酸性细胞瘤和 RCC 亚型，与肿瘤大小无关，是 RCC 转移的潜在预测因子。
