Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor: two variants of a morphologic, immunohistochemical, and genetic distinct entity of renal cell carcinoma.
Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor: two variants of a morphologic, immunohistochemical, and genetic distinct entity of renal cell carcinoma.
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DOI：
10.1097/pas.0000000000000456
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Moch H
中科院分区：
文献类型：
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作者：
Deml KF;Schildhaus HU;Compérat E;von Teichman A;Storz M;Schraml P;Bonventre JV;Fend F;Fleige B;Nerlich A;Gabbert HE;GaBler N;Grobholz R;Hailemariam S;Hinze R;Knüchel R;Lhermitte B;Nesi G;Rüdiger T;Sauter G;Moch H
透明细胞乳头状肾细胞癌 (ccpRCC) 和肾血管平滑肌腺瘤 (RAT) 与透明细胞 (ccRCC) 和乳头状肾细胞癌 (pRCC) 具有形态学相似性。它们的形态学、免疫表型和分子特征是否允许定义单独的肾癌实体存在争议。我们项目的目的是研究参与缺氧诱导因子途径和 VHL 基因突变的特定肾脏免疫组织化学生物标志物，以阐明 ccpRCC 和 RAT 之间的关系。我们使用 25 个标记物通过免疫组织化学研究了 28 个 ccpRCC 和 9 个 RAT 样本。通过桑格测序和荧光原位杂交 (FISH) 研究 VHL 基因突变和等位基因丢失。获得了一部分患者的临床随访数据。在所有患者中均未观察到肿瘤复发或肿瘤相关死亡。免疫组织化学和分子分析将三种肿瘤重新分类为 ccRCC 和 TFE3 易位癌。 ccpRCC 和 RAT 样本的免疫组织化学特征非常相似，但并不完全相同，与 ccRCC 和 pRCC 不同。特别是，与 ccRCC 和 pRCC 相比，ccpRCC/RAT 中的副纤维蛋白和 hKIM-1 表达表现出差异。遗传分析显示，ccpRCC 和 RAT 样本中分别有 2/27 (7%) 和 1/7 (14%) 存在 VHL 突变。 FISH 分析显示 2/20 (10%) ccpRCC 样本中存在 3p 丢失。 ccpRCC 和 RAT 具有特定的形态学和免疫组织化学特征，但它们与更具侵袭性的肾肿瘤有相似之处。根据我们的结果，我们将 ccpRCC/RAT 视为肾细胞癌的一个独特实体。
Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary renal cell carcinoma (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT. We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25 markers. VHL gene mutations and allele losses were investigated by Sanger sequencing and fluorescence in situ hybridization (FISH). Clinical follow-up data were obtained for a subset of the patients. No tumor recurrence or tumor-related death was observed in any of the patients. Immunohistochemistry and molecular analyses led to the reclassification of three tumors as ccRCC and TFE3 translocation carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very similar but not identical, differing from both ccRCC and pRCC. Especially, the parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT compared with ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27 (7%) and 1/7 (14%) ccpRCC and RAT samples, respectively. FISH analysis disclosed a 3p loss in 2/20 (10 %) ccpRCC samples. ccpRCC and RAT have a specific morphologic and immunohistochemical profile but they share similarities with the more aggressive renal tumors. Based on our results, we regard ccpRCC/RAT as a distinct entity of renal cell carcinomas.