高危人类乳头状瘤病毒阳性尿路癌的临床病理学和分子特征描述

Neslihan Kayraklioglu, Bradley A Stohr, Emily Chan
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引用次数: 0

摘要

背景:人乳头瘤病毒(HPV)是导致肛门生殖器和口咽部鳞状细胞癌的一个众所周知的原因,其治疗策略和预后取决于HPV状态。在泌尿道肿瘤中,HPV 状态的重要性尚未得到很好的证实:对HPV+尿路癌(UTC)进行详细的临床、形态学、免疫组化和分子分析:我们发现并回顾性检查了12例经高危HPV原位杂交证实的HPV+ UTC:HPV+UTC来自尿道(9例)和膀胱(3例);12例中有5例(42%)出现结节转移。从形态上看,HPV+ UTC 主要呈基底样;局部可见分化良好的鳞状区。免疫组化(IHC)显示,p16(11 例中的 11 例)、p63(12 例中的 12 例)、细胞角蛋白(CK)903(11 例中的 11 例)和 CK5/6 (11 例中的 11 例)染色较强;GATA3(12 例中的 8 例)和 CK7(11 例中的 4 例)染色不一;尿棘蛋白 II 染色罕见(12 例中的 1 例)。分子分析显示了最常发生改变的基因:KMT2C(42%)、PIK3CA(42%)和KMT2D(25%)。与已发表的常规尿路上皮癌和鳞状细胞癌分子数据相比,TERTp基因突变很少见(8%),也未发现TP53或CDKN2A基因畸变。在现有的随访期间(12 例中有 11 例;中位数为 39 个月),6 例患者因复发而需要治疗;最终,1 例患者死于疾病,2 例患者带病生存,8 例患者无疾病证据。最后,我们提供了11例HPV-鳞状占优势的UTC进行IHC和分子比较;值得注意的是,一部分HPV-UTC的p16 IHC呈阳性(27%),这使得p16 IHC成为该部位HPV状态的特异性较低的替代标记物:HPV+UTC显示出不同的临床、形态和分子特征,表明HPV在UTC中发挥着重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinicopathologic and Molecular Characterization of High-Risk Human Papillomavirus-Positive Carcinomas of the Urinary Tract.

Context.—: Human papillomavirus (HPV) is a well-known cause of squamous cell carcinomas of anogenital and oropharyngeal regions, where treatment strategies and prognosis depend on HPV status. The significance of HPV status in tumors arising along the urinary tract is not well established.

Objective.—: To provide detailed clinical, morphologic, immunohistochemical, and molecular analysis of HPV+ urinary tract carcinomas (UTCs).

Design.—: We identified and retrospectively examined 12 HPV+ UTCs, confirmed by high-risk HPV in situ hybridization.

Results.—: The HPV+ UTCs originated from the urethra (9) and urinary bladder (3); 5 of 12 (42%) presented with nodal metastasis. On morphology, HPV+ UTCs were predominantly basaloid; well-differentiated squamous areas were focally seen. Available immunohistochemistry (IHC) showed strong staining for p16 (11 of 11), p63 (12 of 12), cytokeratin (CK) 903 (11 of 11), and CK5/6 (11 of 11); variable staining for GATA3 (8 of 12) and CK7 (4 of 11); and rare uroplakin II staining (1 of 12). Molecular analysis revealed the most frequently altered genes: KMT2C (42%), PIK3CA (42%), and KMT2D (25%). In contrast to published conventional urothelial and squamous cell carcinoma molecular data, TERTp mutation was rare (8%), and no TP53 or CDKN2A aberrations were identified. During available follow-up (11 of 12; median, 39 months), 6 patients required treatment for recurrence; ultimately, 1 died of disease, 2 were alive with disease, and 8 had no evidence of disease. Finally, we provide 11 HPV- squamous predominant UTCs for IHC and molecular comparisons; notably, a subset of HPV- UTCs was positive for p16 IHC (27%), making p16 IHC a less-specific surrogate marker for HPV status at this site.

Conclusions.—: HPV+ UTCs show distinct clinical, morphologic, and molecular characteristics, suggesting important roles for HPV in UTC.

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