Cytogenetic and Molecular Tumor Profiling for Type 1 and Type 2 Papillary Renal Cell Carcinoma
Cytogenetic and Molecular Tumor Profiling for Type 1 and Type 2 Papillary Renal Cell Carcinoma
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DOI：
10.1158/1078-0432.ccr-08-1229
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发表时间：
2009-02-15
影响因子：
11.5
通讯作者：
Belldegrun, Arie S.
中科院分区：
文献类型：
--
作者：
Klatte, Tobias;Pantuck, Allan J.;Belldegrun, Arie S.
目的：本研究的目的是评估免疫组化和细胞遗传学特征及其预后价值乳头状肾细胞癌（PRCC）subtypes.Experimental Design：一百五十八例PRCC被确定和重新分类的亚型。免疫组化法检测29种分子标志物的表达。对65例患者的前瞻性系列进行了细胞遗传学分析。与临床病理信息和疾病特异性survivals.Results：51例患者（32%）有1型和107（68%）2型PRCC的协会进行了评估。2型患者有更差的东部肿瘤协作组性能状态，更高的T分期，淋巴结和远处转移，更高的级别，和更高的频率坏死，集合系统侵犯和肉瘤样特征。2型显示肿瘤上皮中血管内皮生长因子（VEGF）-R2的表达更高，VEGF-R3在肿瘤上皮和内皮中的表达更高。染色体1 p的丢失，3 p的丢失和5 q的获得仅在2型中观察到，而1型更频繁地具有17三体。2型PRCC的生存率比1型差，但类型并不是独立的预后因素。PTEN、EpCAM、gelsolin、CAN、VEGF-R2和VEGF-R3表达、1 p、3 p或9 p缺失以及17三体缺失均与预后不良相关。结论：2型PRCC具有更侵袭性的临床病理特征和更差的预后。分子和染色体改变可以区分PRCC亚型并影响其预后。在PRCC中3 p缺失对存活的影响与在透明细胞RCC中观察到的关系相反。
Purpose: The goal of this study was to evaluate immunohistochemical and cytogenetic features and their prognostic value in papillary renal cell carcinoma (PRCC) subtypes.Experimental Design: One hundred fifty-eight cases of PRCC were identified and reclassified by subtype. Tumoral expression of 29 molecular markers was determined by immunohistochemistry. Cytogenetic analyses were done on a prospective series of 65 patients. Associations with clinicopathologic information and disease-specific survival were assessed.Results: Fifty-one patients (32%) had type 1 and 107 (68%) type 2 PRCC. Type 2 patients had worse Eastern Cooperative Oncology Group performance status, higherTstages, nodal and distant metastases, higher grades, and a higher frequency of necrosis, collecting system invasion and sarcomatoid features. Type 2 showed greater expression of vascular endothelial growth factor (VEGF)-R2 in the tumor epithelium, and of VEGF-R3 in both tumor epithelium and endothelium. Loss of chromosome 1p, loss of 3p, and gain of 5q were exclusively observed in type 2, whereas type 1 more frequently had trisomy 17. Type 2 PRCC was associated with worse survival than type 1, but type was not retained as an independent prognostic factor. Lower PTEN, lower EpCAM, lower gelsolin, higher CAN, and higherVEGF-R2 and VEGF-R3 expression, loss of 1p, 3p, or 9p, and absence trisomy 17 were all associated with poorer prognosis.Conclusions: Type 2 PRCC is associated with more aggressive clinicopathologic features and worse outcome. Molecular and chromosomal alterations can distinguish between PRCC subtypes and influence their prognosis. The effect of 3p loss on survival in PRCC is opposite to the relationship seen in clear cell RCC.