The retinoblastoma protein/p16INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma
The retinoblastoma protein/p16INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma
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DOI：
10.1111/j.1365-2559.2011.03762.x
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发表时间：
2011-02-01
期刊：
影响因子：
6.4
通讯作者：
Berney, Daniel M.
中科院分区：
文献类型：
--
作者：
Stankiewicz, Elzbieta;Prowse, David M.;Berney, Daniel M.
目的：阴茎鳞状细胞癌（PSCC）的发病机制尚不清楚。人乳头瘤病毒（HPV）可能参与癌变，但很少有研究比较HPV阳性和阴性癌症中细胞周期蛋白的表达。目的是确定不同组织学亚型的PSCC中HPV感染的程度及其对关键细胞周期蛋白表达的影响：p53，p21，p16 INK 4A和视网膜母细胞瘤（RB）protein.Methods和Results：148例PSCC样本进行了化学染色检查RB，p16 INK 4A，p53和p21蛋白表达。通过PCR对102例病例进行了HPV分型。在56%的肿瘤中检测到HPV DNA，其中81%存在HPV 16。基底细胞样肿瘤与HPV感染密切相关（10/13），而疣状肿瘤与HPV感染无关（3/13）。59%（38/64）的普通型SCC有HPV感染。RB蛋白与HPV感染呈负相关（P < 0.0001），p16 INK 4A（P < 0.0001）和p21（P = 0.0002）与HPV感染呈正相关。结论：HPV感染存在于半数以上的阴茎癌中，它是RB通路中断的原因。然而，没有发现HPV和p53免疫检测之间的联系。只有基底细胞和一半的普通型PSSCs与HPV感染相关，证实了这些肿瘤可能的单独病因。
Aims:The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell-cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell-cycle proteins: p53, p21, p16INK4A and retinoblastoma (RB) protein.Methods and results:One hundred and forty-eight PSCC samples were examined immunohistochemically for RB, p16INK4A, p53 and p21 protein expression. One hundred and two cases were typed for HPV by PCR. HPV DNA was detected in 56% of tumours, with HPV16 present in 81%. Basaloid tumours were related strongly to HPV infection (10 of 13), while verrucous were not (three of 13). Fifty-nine per cent (38 of 64) of usual type SCCs had HPV infection. RB protein correlated negatively (P < 0.0001) and p16INK4A (P < 0.0001) and p21 (P = 0.0002) correlated positively with HPV infection. p53 did not correlate with HPV infection.Conclusions:HPV infection is present in more than half of penile cancers and it is responsible for RB pathway disruption. However, no link between HPV and p53 immunodetection was found. Only basaloid and half of usual-type PSSCs correlate with HPV infection, confirming possible separate aetiologies for those tumours.