Willman Joseph H, Heinz David, Golitz Loren E, Shroyer Kenneth R
Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
J Cutan Pathol. 2006 Sep;33(9):629-33. doi: 10.1111/j.1600-0560.2006.00499.x.
Bowen's disease is a form of cutaneous squamous cell carcinoma which may be caused by ultraviolet radiation, human papilloma virus (HPV) infection, or other causes. Although p16 over-expression is a surrogate marker of HPV E7-mediated catabolism of pRb in premalignant and malignant lesions of the cervical mucosa, the correlation of p16 and pRb expression with HPV detection in Bowen's disease has not been well characterized.
A retrospective study on formalin-fixed tissues was performed. Immunohistochemistry for p16 and pRb was performed on 32 cases. DNA was successfully extracted from 20 cases, and polymerase chain reaction was performed to amplify a highly conserved region of the HPV L1 open reading frame.
Twenty-eight of 32 (88%) cases showed strong diffuse staining for p16 but were negative for pRb; two of 32 cases (6%) were negative for p16 but were diffusely positive for pRb; one case was strongly positive for both p16 and pRb, and one case was negative for both p16 and pRb. Three of 20 cases (15%) contained HPV DNA. All three of these cases showed strong p16 expression and lack of pRb staining.
Most cases of Bowen's disease strongly express p16 but not pRb. In contrast to HPV-associated lesions of the cervical mucosa, p16 overexpression in cutaneous Bowen's disease appears to be unrelated to HPV status. The p16 overexpression in Bowen's disease may reflect disruption of the G1/S checkpoint, resulting in unregulated cell cycle progression.
鲍恩病是皮肤鳞状细胞癌的一种形式,可能由紫外线辐射、人乳头瘤病毒(HPV)感染或其他原因引起。虽然p16过表达是宫颈黏膜癌前病变和恶性病变中HPV E7介导的pRb分解代谢的替代标志物,但在鲍恩病中p16和pRb表达与HPV检测之间的相关性尚未得到充分表征。
对福尔马林固定组织进行回顾性研究。对32例病例进行p16和pRb的免疫组织化学检测。成功从20例病例中提取DNA,并进行聚合酶链反应以扩增HPV L1开放阅读框的高度保守区域。
32例病例中有28例(88%)p16呈强弥漫性染色,但pRb为阴性;32例病例中有2例(6%)p16为阴性,但pRb呈弥漫性阳性;1例p16和pRb均为强阳性,1例p16和pRb均为阴性。20例病例中有3例(15%)含有HPV DNA。所有这3例病例均显示p16强表达且缺乏pRb染色。
大多数鲍恩病病例强烈表达p16但不表达pRb。与宫颈黏膜HPV相关病变不同,皮肤鲍恩病中p16过表达似乎与HPV状态无关。鲍恩病中p16过表达可能反映了G1/S检查点的破坏,导致细胞周期进展失控。