Chen Yao-Tseng, Tu Jiangling J, Kao Jean, Zhou Xi K, Mazumdar Madhu
Department of Pathology and Laboratory Medicine, Weill Medical College, Cornell University, New York, NY 10021, USA.
Clin Cancer Res. 2005 Sep 15;11(18):6558-66. doi: 10.1158/1078-0432.CCR-05-0647.
Morphologic distinction among clear cell, papillary, and chromophobe types of renal cell carcinoma (RCC) can be difficult, as is the differential diagnosis between oncocytoma and RCC. Whether these renal tumors can be distinguished by their mRNA expression profile of a few selected genes was examined.
The expression of four genes in renal tumor was evaluated by quantitative reverse transcription-PCR: carbonic anhydrase IX (CA9), methylacyl-CoA racemase (AMACR), parvalbumin (PVALB), and chloride channel kb (CLCNKB). Thirty-one fresh-frozen and 63 formalin-fixed, paraffin-embedded tumor specimens were analyzed.
CA9 expression was highest in clear cell carcinoma and lowest in chromophobe RCC and in oncocytoma. AMACR expression was highest in papillary RCC, and CLCNKB was highest in chromophobe RCC/oncocytoma. PVALB was highest in chromophobe RCC, variable in oncocytoma, and low in clear cell and papillary types. Similar findings were observed in fresh-frozen and formalin-fixed specimens. The mRNA expression ratios among these genes (i.e., CA9/AMACR and AMACR/CLCNKB ratios) further accentuate the gene expression differences among these tumors, and a molecular diagnostic algorithm was established. This algorithm accurately classified the 31 fresh-frozen tumors into 14 clear cell, 5 papillary, 6 chromophobe, and 6 oncocytomas. In the formalin-fixed group, the molecular criteria accurately classified the cases into 15 clear cell, 16 papillary, and 32 in the chromophobe/oncocytoma group but could only separate some, but not all, oncocytomas from chromophobe RCC.
RNA expression ratios based on the four-gene panel can accurately classify subtypes of RCC as well as help distinguish some oncocytomas from chromophobe RCC.
肾细胞癌（RCC）的透明细胞型、乳头状型和嫌色细胞型之间的形态学区分可能存在困难，嗜酸性细胞瘤与RCC的鉴别诊断也同样如此。本研究探讨了能否通过少数选定基因的mRNA表达谱来区分这些肾肿瘤。
通过定量逆转录 - 聚合酶链反应评估肾肿瘤中四个基因的表达：碳酸酐酶IX（CA9）、甲基酰基辅酶A消旋酶（AMACR）、小白蛋白（PVALB）和氯离子通道kb（CLCNKB）。分析了31份新鲜冷冻和63份福尔马林固定、石蜡包埋的肿瘤标本。
CA9在透明细胞癌中的表达最高，在嫌色细胞RCC和嗜酸性细胞瘤中的表达最低。AMACR在乳头状RCC中的表达最高，CLCNKB在嫌色细胞RCC/嗜酸性细胞瘤中的表达最高。PVALB在嫌色细胞RCC中的表达最高，在嗜酸性细胞瘤中变化不定，在透明细胞型和乳头状型中表达较低。在新鲜冷冻标本和福尔马林固定标本中观察到类似的结果。这些基因之间的mRNA表达比率（即CA9/AMACR和AMACR/CLCNKB比率）进一步突出了这些肿瘤之间的基因表达差异，并建立了分子诊断算法。该算法将31份新鲜冷冻肿瘤准确分类为14例透明细胞型、5例乳头状型、6例嫌色细胞型和6例嗜酸性细胞瘤。在福尔马林固定组中，分子标准将病例准确分类为15例透明细胞型、16例乳头状型，以及32例嫌色细胞/嗜酸性细胞瘤组，但只能将部分而非全部嗜酸性细胞瘤与嫌色细胞RCC区分开来。
基于四基因组合的RNA表达比率可准确对RCC亚型进行分类，并有助于将部分嗜酸性细胞瘤与嫌色细胞RCC区分开来。
