Differential expression of the enzyme that esterifies retinol, lecithin:retinol acyltransferase, in subtypes of human renal cancer and normal kidney.
Differential expression of the enzyme that esterifies retinol, lecithin:retinol acyltransferase, in subtypes of human renal cancer and normal kidney.
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发表时间：
2003-10
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通讯作者：
Hui-chun Zhan;L. Gudas;D. Bok;R. Rando;D. Nanus;S. Tickoo
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作者：
Hui-chun Zhan;L. Gudas;D. Bok;R. Rando;D. Nanus;S. Tickoo
类维生素A是一组化合物，包括维生素A（视黄醇）及其相关代谢产物，已被证明可调节多种类型细胞的生长和分化。IFN-α和13-顺式-视黄酸或脂质体全反式视黄酸已用于治疗转移性肾细胞癌患者。我们知道，相对于正常人肾脏样本，肾细胞癌样本中的视黄醇和视黄酯水平大大降低。这促使我们通过免疫组织化学检查LRAT（卵磷脂：视黄醇酰基转移酶）蛋白在各种亚型的人肾癌中相对于正常人肾脏的水平。实验设计：我们检查了1997年至1998年间诊断为肾肿瘤的31例部分或根治性肾切除标本。每个肿瘤的代表性石蜡包埋组织块，每个包含相邻的非肿瘤性肾实质，用于免疫组化分析与亲和纯化的抗体，以人类LRAT蛋白。结果：在正常肾组织和非肿瘤肾组织的肾小球中，LRAT蛋白在肾小管上皮细胞和Bowman囊的内层中呈高水平表达。在31例肿瘤中，常规（透明细胞）肾细胞癌（RCC;包括2例多房囊性RCC）13例，乳头状RCC 7例，嫌色细胞RCC 6例，未分类RCC 1例，肾嗜酸细胞瘤4例。所有肿瘤均显示LRAT的弥漫性免疫反应性。在每种情况下，染色在整个肿瘤中是均匀的，不同区域之间的染色强度仅具有最小的变化。所有4例肾嗜酸细胞瘤、2/6例嫌色细胞RCC、1例常规（透明细胞）癌、1例RCC（未分类）和2例常规RCC（多房囊性型）均为LRAT强染色（3+）。相比之下，剩余的常规RCC和乳头状RCC样品对LRAT的染色强度低得多。在研究中LRAT染色3+的10个肿瘤中，9个是良性肿瘤或恶性潜能低的肿瘤。结论：LRAT在惰性生物学行为的肾肿瘤中表达较高。进一步的研究将确定LRAT是否在肾癌中具有任何预后或治疗作用。
PURPOSE Retinoids, a group of compounds, including vitamin A (retinol), and related metabolites, have been shown to regulate the growth and differentiation of many types of cells. IFN-alpha and either 13-cis-retinoic acid or liposomal all-trans retinoic acid have been used in the treatment of patients with metastatic renal cell carcinoma. We knew that samples from renal cell carcinomas contained greatly reduced levels of retinol and retinyl esters relative to samples from normal human kidney. This prompted us to examine the levels of LRAT (lecithin:retinol acyltransferase) protein in various subtypes of human kidney cancers relative to normal human kidney by immunohistochemistry. EXPERIMENTAL DESIGN We examined 31 partial or radical nephrectomy specimens diagnosed with kidney tumors between 1997 and 1998. Representative paraffin-embedded tissue blocks from each tumor, with each containing adjacent nonneoplastic renal parenchyma, were used for immunohistochemical analysis with affinity purified antibodies to human LRAT protein. RESULTS LRAT protein was detected at high levels in the epithelial cells in the tubules and the lining of Bowman's capsule in the glomeruli of normal, nonneoplastic kidney sections. Among the 31 tumors, there were 13 cases of conventional (clear cell) renal cell carcinoma (RCC; including 2 multilocular cystic RCCs), 7 papillary RCC, 6 chromophobe RCC, 1 RCC, unclassified, and 4 renal oncocytoma. All tumors showed diffuse immunoreactivity for LRAT. In each case, the staining was uniform throughout the tumor, with only minimal variation in the staining intensity between different areas. All 4 renal oncocytomas, 2 of 6 chromophobe RCCs, 1 conventional (clear cell) carcinoma, 1 RCC, unclassified, and 2 conventional RCCs, which were of the multilocular cystic-type stained strongly (3+) for LRAT. In contrast, the remaining conventional RCCs and the papillary RCC samples stained much less intensely for LRAT. Of the 10 tumors that stained 3+ for LRAT in the study, 9 were either benign tumors or tumors with low malignant potential. CONCLUSIONS These data show that LRAT expression is higher in renal tumors with an indolent biological behavior. Additional studies will ascertain if LRAT possesses any prognostic or therapeutic role in renal cancer.