原位杂交检测鲍温样丘疹病及Bowen病中HPV16 DNA

采用生物素标记的核酸探针原位杂交技术,检测了30例鲍温样丘疹病、15例Bowen病中16型人乳头瘤病毒(HPV16)感染的组织定位及染色模式。结果显示,30例鲍温样丘疹病中,HPV16阳性13例;15例Bowen病中,HPV16阳性6例。鲍温样丘疹病、Bowen病中HPV16感染累及棘细胞全层;主要为核内团块状着色。Bowen病中,HPV16感染尚累及基底层细胞且存在HPV的点状染色模式。提示鲍温样丘疹病与Bowen病比较,HPV16感染的组织定位及染色模式均有所不同。     

Detection of papillomavirus capsid antigens and human papillomavirus 16-related DNA in Bowenoid papulosis and Bowen disease

In one out of 22 cases of histologically diagnosed bowenoid papulosis, we could detect human papilloma virus (HPV) capsid antigen in paraffin sections fixed with formalin by means of the peroxidase-antiperoxidase (PAP) test; there were no positive findings regarding biopsies taken from Bowen's disease. Southern blot hybridization technique revealed HPV 16 DNA in 8 out of 10 cases of bowenoid papulosis; there was one positive identification out of 5 cases of Bowen's disease.     

鲍恩样丘疹病中p21和CDK2的表达与人乳头瘤病毒感染的关系

目的:评价鲍恩样丘疹病(Bowenoid populosis,BP)皮损中p21和CDK2的表达与HPV感染的相关性。方法:石蜡包埋标本免疫组化Envision法和IMS细胞图像分析系统分析p21和CDK2蛋白表达。冰冻标本采用煮沸法提取DNA,用导流杂交基因芯片技术作HPV分型检测。结果:在28例BP中p21和CDK2阳性细胞数百分比分别为(31.6±10.5)%和(49.9±13.8)%,显著高于包皮对照组的(22.5±5.4)%和(17.3±8.5)%,P0.05。HPV阳性组p21和CDK2阳性细胞百分比分别为(30.56±11.78)%和(54.42±13.69)%;HPV阴性组p21和CDK2阳性细胞百分比为(33.3±8.36)%和(43.15±11.55)%。p21两组差别无统计学意义(P0.05),而CDK2差别有统计学意义(P0.05)。p21、CDK2直线相关分析无相关性(P0.05)。结论:BP中存在细胞周期相关蛋白的高表达,HPV可能通过作用于细胞周期相关蛋白使细胞周期紊乱,继而导致非典型增生。     

Bowenoid papulosis. Presence of human papillomavirus (HPV) structural antigens and of HPV 16-related DNA sequences

This study reviews 39 cases of anogenital bowenoid papulosis lesions in 22 individuals of both sexes that were analyzed clinically, histologically, immunocytochemically, and virologically. Macroscopically, three different types of lesions were demonstrated: erythematous macules; papules (lichenoid and/or pigmented papules); and leukoplakialike lesions. Microscopically, bowenoid papulosis fulfills the criteria of a squamous cell carcinoma in situ. Much like oral precancers, three distinct growth patterns (flat, endophytic, and exophytic) could be differentiated, which did not correlate with the clinical aspect of the lesions. In only two (5.12%) of the 39 cases of bowenoid papulosis could structural antigens of papillomaviruses be detected immunocytochemically (peroxidase-antiperoxidase technique). The DNA from 12 lesions that were analyzed for the presence of papillomavirus-specific sequences hybridized stringently in all cases with the human papillomavirus 16 specific DNA probe labeled with phosphorus 32.     

Extragenital bowenoid papulosis associated with atypical human papillomavirus genotypes

BACKGROUND: Bowenoid papulosis typically appears as grouped violaceous or red-brown papules in the genital or perianal regions and clinically resembles condylomata acuminata. Isolated extragenital bowenoid papulosis is rare and has been reported in only a few case reports. OBJECTIVES: A 51-year-old immunocompetent, healthy woman had two solitary papules on the elbow; a 41-year-old HIV-positive man had a solitary cutaneous plaque on the abdomen. No genital, periungual, or other extragenital sites of involvement were noted in either patient. The diagnosis was confirmed histologically in both cases. Lesional skin from the female patient was tested with the Digenehybrid HPV DNA assay and was positive for a mixture of low-risk HPV subtypes (6, 11, 42, 43, 44). Lesional skin from the male patient was tested with polymerase chain reaction (PCR). Consensus primers targeted for the HPV L1 region, which is a highly conserved sequence common to more than 20 HPV subtypes encoding a viral capsid protein, were used. PCR using the consensus primers was positive, but type-specific probes for HPV types 6, 11, 16, 18, 45, 31, 33, 35, and 39 were negative. CONCLUSIONS: To our knowledge, our male patient represents the first case of isolated bowenoid papulosis of the abdominal skin. Isolated upper-extremity bowenoid papulosis in our female patient is also a unique case in both location and involvement of low-risk HPV types (6, 11, 42, 43, 44), which have not been previously associated with extragenital bowenoid papulosis.     

Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma

Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR–SSCP) were performed. PCR–SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.     

Detection of human papillomavirus type 16 in bowenoid papulosis and nonbowenoid tissues

A 58‐year‐old Japanese man visited our clinic in December 2000 with a complaint of an erythematous plaque with reddish papules and pigmentation on the penis shaft and glans. He noticed the lesion 1 month before his visit. He denied any previous homosexual activity. His wife denied any genital skin lesion or gynecologic abnormality. No history of human immunodeficiency virus infection could be obtained. Physical examination of the skin lesion revealed an asymptomatic, flat‐topped, approximately 10‐mm‐sized, reddish‐brown keratotic plaque on the penis shaft. It showed an irregular surface, irregular border, and color variegation. Multiple, small, reddish‐brown papules and plaques were distributed on the surrounding penis shaft and glans ( Fig. 1 ). The patient had no symptomatic signs. No lymphadenopathy was noted in the inguinal area.

Figure Figure 1  Open in figure viewer PowerPoint Clinical features of BP lesions on the penis. A keratotic plaque shows an irregular surface, irregular border, and color variegation, and is surrounded by small, reddish‐brown papules     

Bowen's disease on the sole: p16INK4a overexpression associated with human papillomavirus type 16

We report a case of Bowen's disease on the sole presenting clinically as an exophytic, blackish-grey, verrucous tumour, and showing human papillomavirus (HPV) type 16 on analysis with polymerase chain reaction. Positive stains for HPV particles by immunohistochemical analysis were limited to several cell nuclei at the upper stratum Malpighii. However, all the tumour cells in the epidermis exhibited strong and diffuse nuclear and cytoplasmic stains for the tumour suppressor protein p16INK4a. We speculate that dysregulation of the retinoblastoma/p16INK4a pathway may be involved in the pathogenesis of the lesion, and p16INK4a overexpression might serve as a useful surrogate marker for identifying Bowen's disease harbouring high-risk types of HPV infection.     

Expression of p16 protein in acral lentiginous melanoma

Background Acral lentiginous melanoma (ALM) is a clinicopathologic subtype of cutaneous malignant melanoma. ALM is the most common type of melanoma amongst Asians, Africans, and patients with mixed ancestry. In Brazil, ALM comprises 10% of cutaneous melanoma. ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant. Alterations and inactivation of the p16INK4 gene that encodes a specific inhibitor of cyclin‐dependent kinase have been related to melanoma genesis and progression. Few studies, however, have addressed p16 expression in ALM. Methods In order to verify and compare p16 protein expression, 32 paraffin‐embedded ALM specimens were subjected to a immunohistochemical technique using a monoclonal anti‐p16 antibody. The tumors were classified according to thickness (up to 1.0 mm and thicker than 1.0 mm) and the presence of ulceration. Results Twenty‐five (78%) ALMs displayed positive p16 protein expression: 21 of the 25 (84%) with a thickness of more than 1.0 mm, and four of the seven (57%) with a thickness of 1.0 mm or less. Thirteen of the 17 (76%) nonulcerated lesions and 12 of the 15 (80%) ulcerated lesions displayed positive p16 protein expression. Conclusion The data obtained suggest that p16 protein expression per se may not represent a marker of retinoblastoma protein (pRb) pathway disturbance in ALM tumorigenesis.