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NKX6-1 Is a Less Sensitive But Specific Biomarker of Chromophobe Renal Cell Carcinoma
The American Journal of Surgical Pathology ( IF 5.6 ) Pub Date : 2022-06-01 , DOI: 10.1097/pas.0000000000001872
Bin Xie 1 , Kuo Tong 2 , Jiao Yang 3 , Taoli Wang 4 , Lingchao Cheng 1 , Suimin Zeng 5 , Zhongliang Hu 1, 6
Affiliation  

NKX6-1 is a transcription factor that plays a key role in the development, differentiation, and identity maintenance of beta cells of pancreatic islets. Although NKX6-1 expression has also been discovered in pancreatic well-differentiated neuroendocrine tumors (WDNETs) and duodenal WDNETs, its expression in chromophobe renal cell carcinoma (chRCC) is unexplored. Analysis of mRNA expression and immunohistochemistry of NKX6-1 was performed using the kidney cancer cohort from The Cancer Genome Atlas (TCGA) and paraffin-embedded whole-tissue slides from our 196 collected cases, including 48 chRCCs (43 classic and 5 eosinophilic subtypes), 24 renal oncocytomas (ROs), 46 clear cell renal cell carcinomas, 41 papillary renal cell carcinomas, 14 renal urothelial carcinomas, 7 low-grade oncocytic renal tumors (LOTs), 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. NKX6-1 expression was almost exclusively upregulated in chRCC at both the mRNA and protein levels compared with other renal tumors. NKX6-1 was immunohistochemically positive in 39 of 48 (81.3%) chRCCs, but negative in 46 clear cell renal cell carcinomas, 24 ROs, 7 low-grade oncocytic renal tumors, 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. Diffuse, moderate, and focal NKX6-1 staining were seen in 21, 4, and 14 of the 39 chRCCs, respectively. In contrast, NKX6-1 was focally positive in only 1 of 41 (2.4%) papillary renal cell carcinomas and 2 of 14 (14.3%) renal urothelial carcinomas. Therefore, the sensitivity and specificity of NKX6-1 staining were 81.3% and 98% for chRCC, respectively. In conclusion, NKX6-1 may be a novel potential marker for differentiating chRCC from other renal neoplasms, especially from RO.



中文翻译:

NKX6-1 是一种不太敏感但特异的嫌色肾细胞癌生物标志物

NKX6-1 是一种转录因子,在胰岛 β 细胞的发育、分化和身份维持中起关键作用。尽管在胰腺高分化神经内分泌肿瘤 (WDNET) 和十二指肠 WDNET 中也发现了 NKX6-1 的表达,但它在嫌色肾细胞癌 (chRCC) 中的表达尚未探索。NKX6-1 的 mRNA 表达和免疫组织化学分析使用癌症基因组图谱 (TCGA) 的肾癌队列和来自我们收集的 196 个病例的石蜡包埋全组织切片进行,包括 48 个 chRCC(43 个经典亚型和 5 个嗜酸性亚型) , 24 例肾嗜酸细胞瘤 (RO), 46 例透明细胞肾细胞癌, 41 例乳头状肾细胞癌, 14 例肾尿路上皮癌, 7 例低级别嗜酸细胞肾肿瘤 (LOT), 8 例嗜酸性实体和囊性肾细胞癌、3 例琥珀酸脱氢酶缺陷型肾细胞癌和 5 例肾嗜酸细胞肿瘤,未另作说明。与其他肾肿瘤相比,在 chRCC 中 NKX6-1 的表达几乎完全在 mRNA 和蛋白质水平上调。NKX6-1 在 48 例 (81.3%) chRCC 中的 39 例免疫组化阳性,但在 46 例透明细胞肾细胞癌、24 例 RO、7 例低级别嗜酸细胞肾肿瘤、8 例嗜酸性实体和囊性肾细胞癌、3 例琥珀酸脱氢酶-缺陷型肾细胞癌和 5 例肾嗜酸细胞肿瘤,未另作说明。39 个 chRCC 中的 21 个、4 个和 14 个分别观察到弥漫性、中度和局灶性 NKX6-1 染色。相比之下,NKX6-1 在 41 例 (2.4%) 乳头状肾细胞癌中仅 1 例和 14 例中的 2 例 (14. 3%) 肾尿路上皮癌。因此,NKX6-1 染色对 chRCC 的敏感性和特异性分别为 81.3% 和 98%。总之,NKX6-1 可能是区分 chRCC 与其他肾肿瘤,尤其是 RO 的新的潜在标志物。

更新日期:2022-05-31
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