Extragenital Bowen's Disease Research Articles

Association of human papillomavirus and extra-genital Bowen disease (squamous cell carcinoma in situ): A systematic review

Association of human papillomavirus and extra-genital Bowen disease (squamous cell carcinoma in situ): A systematic review

Extragenital Human Papillomavirus 16-associated Bowen's Disease.

Extragenital Human Papillomavirus 16-associated Bowen's Disease.

Low Rate of Detection of Mucosal High-Risk-Type Human Papillomavirus in Korean Patients with Extragenital Bowen's Disease and Squamous Cell Carcinoma, Especially in Digital Cases

Human papillomavirus (HPV) infection has been demonstrated in some of the nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease through, if any, digital-genital transmission. We screened for the presence of the mucosal HPV DNA in patients with extragenital Bowen's disease (n = 30), squamous cell carcinoma (n = 11), bowenoid papulosis (n = 9), verrucous carcinoma (n = 1), actinic keratosis (n = 5), and basal cell carcinoma (n = 5). We used a PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping data was confirmed using a conventional direct DNA sequencing method. Two cases of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. None of the squamous cell carcinoma cases were positive. Neither patients with digital Bowen's disease (n = 5) nor those with squamous cell carcinoma (n = 3) showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was confirmed in 5 (55.6%) of the 9 patients with bowenoid papulosis. HPV 16 was most prevalent (n = 3), while the DNA of HPVs 35 and 67 was detected in one sample for each of the two types. Our study demonstrated that two (6.7%) of the patients with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease. However, we could not find any relationship between the mucosal high-risk HPV and Bowen's disease or squamous cell carcinoma in the fingers.

Photoexposition discriminates Notch 1 expression in human cutaneous squamous cell carcinoma

The Notch signaling pathway may play opposing roles in cancer. It can be oncosuppressive or protumoral, depending on the cellular and tissue context. In skin cancer, Notch 1 expression is downregulated, thus supporting the hypothesis of an oncosuppressive role in cutaneous carcinomas. However, as members of the Notch family undergo downregulation upon exposure to UV irradiation, we wondered whether Notch 1 expression in skin carcinomas may be governed by additional factors, including UV exposure. We investigated the expression of Notch 1 and its ligands, Jagged 1, Jagged 2 and Delta-like 1, by immunohistochemistry in a series of premalignant and invasive cutaneous carcinomas, including 4 solar keratoses, 5 Bowen's disease, 5 squamous cell carcinomas on sun-exposed skin, 6 squamous cell carcinomas on sun-protected genital skin and 14 basal cell carcinomas of different histotypes (nodular, superficial type, sclerodermiform/infiltrating and baso-squamous). Expression of Notch 1 was decreased in solar keratoses and invasive squamous cell carcinomas localized on sun-exposed skin. In contrast, marked Notch 1 staining was observed in extragenital Bowen's disease as well as in genital (penile) human papilloma virus-related in situ and invasive squamous cell carcinomas. A diffuse Notch 1 staining was detected in nodular and superficial basal cell carcinomas while sclerodermiform/infiltrating and baso-squamous basal cell carcinomas showed a low to absent Notch 1 expression. Jagged 1, Jagged 2 and Delta-like 1 proteins were expressed in all tissues examined. Present findings show divergent expression of Notch 1 in skin cancer, depending on anatomical site and tumor histotype. Thus, whereas in UV-related squamous cell photocarcinogenesis Notch 1 downregulation could mirror a tumor suppressor function of the receptor, in sun-protected squamous cell carcinomas Notch 1 was upregulated. Furthermore, Notch 1 expression was minimal in basal cell carcinoma subtypes correlated with risk of recurrence (sclerodermiform/infiltrating and baso-squamous) in comparison with nodular and superficial types.

Human papillomaviruses of the mucosal type are present in some cases of extragenital Bowen's disease

Bowen's disease in the genital area is generally considered to be caused by mucosal high-risk human papillomaviruses (HPVs). However, the detection rate and spectrum of HPVs in extragenital Bowen's disease are various and it is not clear to what extent HPV is involved in its pathogenesis. To assess the degree of association of HPV in extragenital cases by examining detection rates, types, quantities and localization of HPV. A polymerase chain reaction (PCR) approach that we had previously established, which can give sensitive detection of a broad range of HPVs from cutaneous [including epidermodysplasia verruciformis-related HPVs (EV-HPVs)] to mucosal HPVs, was applied to samples from 41 patients with extragenital Bowen's disease and normal skin samples from 48 individuals. Semiquantitative L1-PCR and tyramide-based in situ hybridization (ISH) were also employed for positive cases. HPVs belonging to the mucosal high-risk group were detected in three patients with Bowen's disease (7%; two HPV 16 and one HPV 33), with 10(1)-10(3) copy equivalents per diploid amount of cellular DNA. They were distributed among most nuclei of tumour cells but in none of the cells of adjacent normal skin. HPVs belonging to the cutaneous group were detected in two patients (5%; HPV 27 and HPV 76) at 10(-2)-10(-3) copy equivalents, the same level as in a normal skin specimen positive for type 23 EV-HPV. No positive signals were observed by ISH. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease.

Human herpes viruses in non-melanoma skin cancers.

We examined the possible involvement of human herpes viruses in sporadic non-melanoma skin cancer of Greek patients. Polymerase chain reaction (PCR) based detection assays were utilized for the detection of viral cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) genomes in 24 squamous cell carcinomas (SCC), five Bowen's disease, 72 basal cell carcinomas (BCC) specimens and eight premalignant lesions. Forty-two of 109 (38.5%) skin lesions were found positive for CMV DNA. The highest incidence was 6/8 (75%) observed in specimens with premalignant lesions. The incidence was 37.5% (27/72) in BCC, 33% (8/24) in SCC and 20% (1/5) in extragenital Bowen's disease. All samples were negative for HSV-1/2 and EBV DNA as assessed by our PCR based assay. The CMV infection showed no statistically significant correlation with the histological type, age, site of lesion or sex. Our results give a strong indication of the possible involvement of CMV in non-melanoma skin cancer development.

Mucosal oncogenic human papillomaviruses and extragenital Bowen disease

Genital Bowen disease is known to have a strong association with human papillomavirus (HPV) type 16. On the other hand, previous studies of extragenital Bowen disease (EBD) that have used different hybridization techniques have produced discordant results in the detection of mucosal oncogenic HPV. Ninety-four samples of EBD from 78 patients were investigated clinicopathologically. DNA extracted from fixed and embedded tissues was analyzed for the presence of the main mucosal oncogenic HPV types 16, 18, 31, and 33 using polymerase chain reaction (PCR) with specific primers described in 1996 by Baay et al., which are particularly well adapted to fixed tissues and give small amplimers. Moreover, 11 EBD of the hands were investigated by in situ hybridization (ISH). Of the 94 extragenital BD obtained from 78 patients, HPV DNA type 16 was detected in 78 cases (83%) from 65 patients (83.3%) by PCR. Nine patients with EBD of the hands (90%) had HPV type 16, and ISH displayed a diffuse hybridization pattern that corresponded to the episomal viral form of HPV DNA. The current retrospective study of 94 samples clearly demonstrates the high prevalence of HPV type 16 infection in EBD, especially in EBD of the hands. In this study, no specific clinical, topographic, or histopathologic features of any lesions were found to be indicative of the presence or absence of HPV.

Mucosal oncogenic human papillomaviruses and extragenital Bowen disease

Mucosal oncogenic human papillomaviruses and extragenital Bowen disease

Expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67 in benign, premalignant and malignant skin lesions with implicated HPV involvement.

A series of 120 biopsies from benign (verruca vulgaris and keratoacanthoma), premalignant (actinic keratosis and extragenital Bowen's disease) and malignant (squamous cell carcinoma) skin lesions were studied immunohistochemically for the expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67. The presence of human papillomavirus (HPV) DNA in these samples had been analysed previously using in situ hybridization (ISH) and PCR. Moderate to intense expression of both PCNA and Ki-67 was present in most of the lesions studied. PCNA staining was extensive in the epidermis underneath the layers where abundant HPV DNA staining was shown in HPV DNA-positive verrucas. In keratoacanthomas, p21 and PCNA expression remained low, despite intense p53 expression. In actinic keratosis, only half of the specimens showed overexpression of p53 associated with moderate or intense expression of PCNA. In extragenital Bowen's lesions, all these cell-cycle markers were overexpressed, but in squamous cell carcinomas, they were heterogeneously expressed and showed no correlation with tumour differentiation. Our results suggest a mechanism by which HPV can reactivate the host genes (leading to cell proliferation) to support its own DNA replication. Also p21 might start keratinocyte differentiation in areas where HPV DNA replication starts. Cell proliferation remained active in actinic keratosis and Bowen's lesions, emphasizing the precancer character of these lesions in contrast with the benign nature of keratoacanthoma and verruca vulgaris.

Failure to demonstrate human papillomavirus (HPV) involvement in Bowen's disease of the skin.

To assess the role of human papillomavirus (HPV) in the aetiology of extragenital Bowen's disease (EBD), a series of 91 cases were analysed using in situ hybridization (ISH) with whole genomic DNA probes of HPV types 1, 2, 4, 6, 7, 11, 12, 15, 16, 18, 26, 36, 37, 39, 42, 55 and 59. No HPV DNA was found in any of the samples tested. A polymerase chain reaction (PCR) was also used to analyse 37 of the 91 samples, using both the consensus primers MY09/MY11 which amplify a large number of HPV types from the L1 region and the degenerate primers CP65/CP70, which amplify the complete set of epidermodysplasia verruciformis (EV) HPV types. All the cases were also negative in the PCR. The results suggest that EBD is not HPV-related, at least in immunocompetent patients.

Detection of human papillomavirus in extragenital Bowen's disease using in situ hybridization and polymerase chain reaction.

Extragenital Bowen's disease (EBD) has rarely been studied for the presence of human papillomaviruses (HPVs). Twenty consecutive patients with EBD were investigated for the presence of HPVs using in situ hybridization with a generic probe that can detect HPV DNA types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52 and specific probes for HPV DNA types 6/11, 16/18, and 31/33/35. All cases were tested with the polymerase chain reaction (PCR) technique employing the L1 consensus primer pair, MY11 (primer for the positive strand) and MY9 (primer for the negative strand) complementary to genital and dermal HPV types. Seven caucasian patients, five males and two females, with an average age of 70.4 years, showed positive in situ hybridization (ISH) for HPV DNA. The positivity varied from 5 to 40% of neoplastic cells. Three of seven of the ISH DNA-positive cases showed a positive PCR for DNA HPVs. The role of HPVs in human tumors is not fully understood since oncogenic types of HPVs have been found in normal tissue and the actions of cofactors have been postulated. Bowen's disease usually occurs in elderly people in whom the efficiency of the immune systems may be compromised. The association between HPV infection and low efficiency of the immune response may be responsible for HPV-related Bowen's disease in elderly people.

Human papillomavirus infection and filaggrin expression in paraffin-embedded biopsy specimens of extragenital Bowen's disease and genital bowenoid papulosis

Cutaneous Bowen's disease (BD) and genital bowenoid papulosis (BP) are considered as precancerous or cancerous lesions that are sometimes infected with human papillomavirus (HPV). We studied retrospectively paraffin-embedded sections of 11 samples of cutaneous BD and 6 samples of genital BP from the general population for HPV infection and filaggrin expression. Using in situ hybridization with biotinylated probes of HPV types 1, 2, 5, 6, 11, 16, and 18, under stringent and/or non-stringent conditions and a streptavidin-alkaline-phosphatase complex for hybrid detection, HPV DNA was detected in 6/17 cases (5 BD and 1 BP). Positive nuclei were located in intermediate or upper epithelial cell layers. HPV 16 was found in 2 cases of BD but associated either with HPV 2 or 18. Three additional lesions reacted only under non-stringent conditions; HPV could not be typed with the probes used. The positive case of BP reacted with the four probe types 1, 2, 16, 18 and was negative with HPV 6 or 11. Viral antigen was not detected by indirect immunofluorescence with a rabbit antiserum directed to group-specific viral capsid antigen. Differentiation disorders were observed in the intermediate and upper cell layers of these specimens, as shown by a reduced expression of filaggrin/profilaggrin, a marker of terminal differentiation, in extragenital BD (7/11 cases), and an increased expression in genital BP (4/5 cases) although viral DNA was not always detectable. This study shows that in situ hybridization is a valuable technique for HPV DNA detection and its typing in BD and BP lesions on deparaffinized sections. The positive nuclei were located in the cell layers that exhibited abnormal expression of differentiation. There is no relation between the HPV infecting type and the filaggrin expression.

Immunohistochemistry (S 100, KL 1) and human papillomavirus DNA hybridization on Morbus Bowen and bowenoid papulosis

In this study 55 paraffin embedded samples defined as Bowen's disease or bowenoid papulosis were investigated with antibodies against S 100 protein and keratins (KL 1). S 100-positive cells were quantified and related to defined section area of the epidermal compartment by computer-assisted image analysis. The density of S 100-positive cells was compared with normal skin and was particularly related to growth patterns and keratinization of the different lesions under study. S 100-positive dendritic cells were found to be reduced overall in bowenoid lesions when compared with normal skin. Lesions with high counts of S 100-positive dendritic cells most frequently showed a solitary growth pattern with highly conserved architecture and differentiation and no tendency to stromal invasion. In contrast, cases with low counts of S 100-positive cells very often showed multifocal development, a high degree of architectural disturbance and dedifferentiation. In this group, stromal invasion (cases of invasive carcinoma associated with Bowen's disease) was seen more often. Interestingly, this latter group of cases also revealed a peculiar keratin pattern. Frequently, the basal cell layer was decorated with KL 1 antibody, which usually recognizes only suprabasaly located keratinocytes. No differences between Bowen's disease and bowenoid papulosis were found in terms of densities of S 100-positive dendritic cells and keratin pattern. In our experience, extragenital Bowen's disease and genital Bowen's disease can not be distinguished on purely morphological grounds or with the immunocytochemical approach presented here. Interestingly, when employing in situ hybridization with HPV 16 probes three of seven samples of genital Bowen's disease harboured HPV 16 DNA, whereas six cases of extragenital disease were negative.