Kauffman E C, Barocas D A, Chen Y T, Yang X J, Scherr D S, Tu J J
Department of Urology, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, New York, USA.
J Urol. 2009 May;181(5):2305-11. doi: 10.1016/j.juro.2009.01.003. Epub 2009 Mar 19.
The similar appearance of renal tumor histological subtypes can complicate differential diagnoses. This problem is most notable for the chromophobe subtype of renal cell carcinoma, which can be histologically indistinguishable from oncocytoma with investigational molecular markers failing to provide reliable differentiation. KAI1 is a metastasis suppressor gene whose expression correlates inversely with the metastatic potential of most solid tumor cancer types. We tested the hypothesis that KAI1 is differentially expressed among renal tumor histological subtypes.
Immunohistochemical staining for KAI1 protein was performed in 152 nephrectomy specimens, including 48 clear cell, 35 papillary and 31 chromophobe renal cell carcinoma samples, 28 oncocytomas and 10 tumor-free kidneys. Staining was scored as none/minimal, low, moderate or high. KAI1 mRNA levels were compared by quantitative reverse transcriptase-polymerase chain reaction in an additional 22 chromophobe renal cell carcinoma and oncocytoma samples.
In all 10 tumor-free kidneys KAI1 protein was detected exclusively in distal tubule cell membranes. Of the tumor specimens KAI1 protein was absent in all papillary renal cell carcinoma specimens. It was present in only 1 of 48 clear cell renal cell carcinomas (2%) and 2 of 28 oncocytomas (7%) but only at low levels. In contrast, 27 of 31 chromophobe renal cell carcinoma specimens (87%) expressed KAI1 protein, most at moderate or high levels. The diagnostic accuracy of KAI1 immunostaining for discerning chromophobe renal cell carcinoma from oncocytoma was 90% with similar results observed at the RNA level.
KAI1 is an accurate biomarker for chromophobe renal cell carcinoma that may aid in the diagnostic differentiation of chromophobe renal cell carcinoma from oncocytoma. It remains to be determined whether KAI1 expression contributes to the low metastatic potential of chromophobe renal cell carcinoma.
肾肿瘤组织学亚型的相似外观会使鉴别诊断复杂化。这个问题在肾细胞癌的嫌色细胞亚型中最为显著，该亚型在组织学上与嗜酸细胞瘤难以区分，且研究用的分子标志物也无法提供可靠的鉴别依据。KAI1是一种转移抑制基因，其表达与大多数实体瘤癌症类型的转移潜能呈负相关。我们检验了KAI1在肾肿瘤组织学亚型中差异表达的假说。
对152例肾切除标本进行KAI1蛋白的免疫组织化学染色，包括48例透明细胞肾细胞癌、35例乳头状肾细胞癌和31例嫌色细胞肾细胞癌样本、28例嗜酸细胞瘤及10例无肿瘤肾脏。染色分为无/极少、低、中、高四个等级。另外，通过定量逆转录-聚合酶链反应比较22例嫌色细胞肾细胞癌和嗜酸细胞瘤样本中的KAI1 mRNA水平。
在所有10例无肿瘤肾脏中，KAI1蛋白仅在远端肾小管细胞膜中检测到。在肿瘤标本中，所有乳头状肾细胞癌标本均未检测到KAI1蛋白。在48例透明细胞肾细胞癌标本中仅1例（2%）、28例嗜酸细胞瘤标本中仅2例（7%）检测到KAI1蛋白，且均为低水平表达。相比之下，31例嫌色细胞肾细胞癌标本中有27例（87%）表达KAI1蛋白，大多数为中等或高水平。KAI1免疫染色鉴别嫌色细胞肾细胞癌与嗜酸细胞瘤的诊断准确率为90%，在RNA水平也观察到类似结果。
KAI1是嫌色细胞肾细胞癌的一种准确生物标志物，可能有助于嫌色细胞肾细胞癌与嗜酸细胞瘤的诊断鉴别。KAI1表达是否导致嫌色细胞肾细胞癌转移潜能低仍有待确定。
