Samanta Minu, Harkins Lualhati, Klemm Katrin, Britt William J, Cobbs Charles S
Surgical Service, Veterans Affairs Medical Center, University of Alabama at Birmingham, Birmingham, AL, USA.
J Urol. 2003 Sep;170(3):998-1002. doi: 10.1097/01.ju.0000080263.46164.97.
Recent epidemiological data indicate that a history of increased exposure to sexually transmitted diseases is associated with an increased risk of prostate cancer. Human cytomegalovirus (HCMV) is a member of the herpesvirus family, is sexually transmitted in adults and can persistently infect prostatic epithelium in non-immunocompromised hosts. Based on increased awareness of the oncogenic potential of this virus, we decided to reexplore the issue of whether HCMV might be involved in prostate cancer pathogenesis.
Paraffin embedded biopsy specimens from 22 randomly selected patients with prostatic intraepithelial neoplasia (PIN) lesions and prostatic carcinoma were analyzed by immunohistochemistry, in situ hybridization, polymerase chain reaction and DNA sequencing to detect HCMV nucleic acids and determine whether HCMV gene products were specifically associated with neoplastic cells.
We detected HCMV proteins and/or nucleic acids in all 22 of the 22 preneoplastic and neoplastic prostate lesions evaluated. HCMV proteins were specifically and often highly expressed in basal cell hyperplasia and PIN lesions, and to a lesser degree in carcinoma cells.
To our knowledge these data demonstrate for the first time the specific localization of HCMV nucleic acids and proteins in a high percent of PIN and prostate carcinoma lesions, and raise the possibility that HCMV might contribute to the natural history of prostatic cancer.
近期流行病学数据表明,性传播疾病暴露史增加与前列腺癌风险升高相关。人巨细胞病毒(HCMV)是疱疹病毒家族的一员,在成年人中可通过性传播,并且能在非免疫功能低下的宿主中持续感染前列腺上皮。基于对该病毒致癌潜力认识的增加,我们决定重新探讨HCMV是否可能参与前列腺癌发病机制这一问题。
对22例随机选取的前列腺上皮内瘤变(PIN)病变和前列腺癌患者的石蜡包埋活检标本进行免疫组织化学、原位杂交、聚合酶链反应及DNA测序分析,以检测HCMV核酸,并确定HCMV基因产物是否与肿瘤细胞特异性相关。
在评估的所有22例前列腺癌前病变和肿瘤性病变中,我们均检测到了HCMV蛋白和/或核酸。HCMV蛋白在基底细胞增生和PIN病变中特异性且常呈高表达,在癌细胞中的表达程度较低。
据我们所知,这些数据首次证明了HCMV核酸和蛋白在高比例的PIN和前列腺癌病变中的特异性定位,并提出了HCMV可能参与前列腺癌自然病程的可能性。