Clear Cell Papillary Renal Cell Carcinoma and Renal Angiomyoadenomatous Tumor: Two Variants of a Morphologic, Immunohistochemical, and Genetic Distinct Entity of Renal Cell Carcinoma.
透明细胞乳头状肾细胞癌和肾血管平滑肌腺瘤样肿瘤:形态学、免疫表型和遗传学上均为肾细胞癌的两种独立实体亚型
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
Abstract
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.
摘要
透明细胞乳头状肾细胞癌(ccpRCC)和肾血管平滑肌腺瘤样肿瘤(RAT)在形态学上与透明细胞肾细胞癌(ccRCC)和乳头状RCC(pRCC)有许多相似之处。目前争论的问题是,从他们的形态学、免疫表型和分子学特征上能否将其定义为独立的肾细胞癌实体。本研究的目的在于调查涉及缺氧诱导因子通路和VHL基因突变中的特异性肾免疫组化标记物,来阐明ccpRCC和RAT的关联。作者在28例ccpRCC和9例RAT样本中研究了25种标记物的免疫组化表达情况,并通过Sanger测序法和荧光原位杂交研究了VHL基因的突变和等位基因的缺失情况。可获得部分患者的临床随访情况。任何患者均未出现肿瘤复发或肿瘤相关性死亡。通过免疫组化和分子学分析,3例肿瘤被重新分类为ccRCC和TFE3易位性肾癌。ccpRCC和RAT样本的免疫组化非常相似,但不完全相同,不同于ccRCC和pRCC。特别是parafibromin和hKIM-1在ccpRCC/RAT中的表达,与ccRCC和pRCC相比,有很大的差别。遗传性分析显示2/27 (7%) 的ccpRCC 和1/7 (14%)的RAT 样本中有VHL突变。荧光原位杂交分析显示2/20 (10%) ccpRCC样本中存在3p缺失。ccpRCC和RAT有独特的形态学和免疫表型特征,但和其它侵袭性强的肾肿瘤相比,也有许多相似性。建立在以上研究的基础上,作者认为ccpRCC/RAT是RCCs独立的实体。
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