Zhu K W, Affolter V K, Gaynor A M, Dela Cruz F N, Pesavento P A
Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA
Vet Pathol. 2015 Nov;52(6):1067-72. doi: 10.1177/0300985815583095. Epub 2015 May 12.
Equus caballus papillomavirus 2 (EcPV2) has been proposed as an etiologic agent for genital squamous cell carcinoma (SCC), the most common malignant tumor of the horse penis. EcPV2 is commonly detected by polymerase chain reaction (PCR) on normal horse genitalia; therefore, unraveling the virus' role in oncogenic transformation requires other methods of detection. In this study, a highly sensitive multiple-probe chromogenic in situ hybridization (ISH) technique was designed to recognize the E6/E7 oncogenes of EcPV2. ISH demonstrated abundant virus within 6 of 13 penile and preputial SCCs, whereas evidence of solar damage was found in 6 cases that were negative for EcPV2 by ISH. The ISH technique is valuable for studies of pathogenesis, since it demonstrates for the first time that the vast majority of neoplastic cells contain virus. Moreover, hybridization was present in all metastases examined, implying stability of E6/E7 expression in these clonal populations of neoplastic cells. This study contributes to the accumulating evidence for a causal role of EcPV2 in a subset of genital SCCs in horses.
马乳头瘤病毒2型(EcPV2)已被提出是马阴茎最常见的恶性肿瘤——生殖器鳞状细胞癌(SCC)的病原体。EcPV2通常通过对正常马生殖器进行聚合酶链反应(PCR)检测到;因此,要阐明该病毒在致癌转化中的作用需要其他检测方法。在本研究中,设计了一种高灵敏度的多探针显色原位杂交(ISH)技术来识别EcPV2的E6/E7癌基因。ISH显示,在13例阴茎和包皮SCC中有6例存在大量病毒,而在ISH检测EcPV2呈阴性的6例病例中发现了日光损伤证据。ISH技术对发病机制研究很有价值,因为它首次证明绝大多数肿瘤细胞含有病毒。此外,在所有检测的转移灶中均存在杂交信号,这意味着这些肿瘤细胞克隆群体中E6/E7表达具有稳定性。本研究为EcPV2在马的一部分生殖器SCC中起因果作用的证据积累做出了贡献。