Deml Karl-Friedrich, Schildhaus Hans-Ulrich, Compérat Eva, von Teichman Adriana, Storz Martina, Schraml Peter, Bonventre Joseph V, Fend Falko, Fleige Barbara, Nerlich Andreas, Gabbert Helmut E, GaBler Nikolaus, Grobholz Rainer, Hailemariam Seife, Hinze Raoul, Knüchel Ruth, Lhermitte Benoit, Nesi Gabriella, Rüdiger Thomas, Sauter Guido, Moch Holger
*Institute of Surgical Pathology, University Hospital Zurich, Zurich ‡‡Cantonal Hospital Aarau §§Institute of Histological and Cytological Diagnostics, Aarau ¶¶University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland †Institute of Pathology, University Medicine Göttingen (UMG), Göttingen ∥Institute of Pathology, University Hospital Tübingen, Tübingen ¶Institute of Pathology, HELIOS Hospital Berlin-Buch, Berlin #Institute of Pathology Bogenhausen, Städtisches Klinikum München GmbH, Munich **Institute of Pathology, Heinrich Heine University Hospital, Dusseldorf ††Institute of Pathology, RWTH University, Aachen ∥∥Institute of Pathology, HELIOS Hospital Schwerin, Schwerin ***Institute of Pathology, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe †††Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ‡Service d'Anatomie et Cytologie Pathologiques 1, Groupe Hospitalier Pitié-Salpêtrière, Paris, France §Department of Medicine, Renal Division, Brigham and Women's Hospital, Boston, MA ##Institute of Pathology, University of Florence, Florence, Italy.
Am J Surg Pathol. 2015 Jul;39(7):889-901. doi: 10.1097/PAS.0000000000000456.
Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary RCC (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. 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 3 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. Fluorescence in situ hybridization 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. On the basis of our results, we regard ccpRCC/RAT as a distinct entity of RCCs.
透明细胞乳头状肾细胞癌（ccpRCC）和肾血管肌腺瘤性肿瘤（RAT）在形态学上与透明细胞肾细胞癌（ccRCC）和乳头状肾细胞癌（pRCC）相似。它们的形态学、免疫表型和分子特征是否能定义一个独立的肾癌实体仍存在争议。我们项目的目的是研究参与缺氧诱导因子途径的特定肾免疫组化生物标志物以及VHL基因的突变，以阐明ccpRCC与RAT之间的关系。我们使用25种标志物通过免疫组化对28例ccpRCC和9例RAT样本进行了研究。通过桑格测序和荧光原位杂交研究了VHL基因突变和等位基因缺失情况。获得了部分患者的临床随访数据。所有患者均未观察到肿瘤复发或肿瘤相关死亡。免疫组化和分子分析导致3例肿瘤重新分类为ccRCC和TFE3易位癌。ccpRCC和RAT样本的免疫组化特征非常相似但并不完全相同，与ccRCC和pRCC均不同。特别是，与ccRCC和pRCC相比，副纤维蛋白和hKIM-1表达在ccpRCC/RAT中表现出差异。基因分析显示，ccpRCC和RAT样本中VHL突变分别为2/27（7%）和l/7（14%）。荧光原位杂交分析显示2/20（10%）的ccpRCC样本存在3p缺失。ccpRCC和RAT具有特定的形态学和免疫组化特征，但它们与侵袭性更强的肾肿瘤有相似之处。基于我们的研究结果，我们将ccpRCC/RAT视为一种独特的肾癌实体。
