Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed the p53 protein expression and gene mutations to evaluate the role of ultraviolet radiation or other carcinogens, and possible racial differences in 17 samples from 12 Korean patients with Bowen's disease. A simple microdissection technique was used to collect the tumor cells selectively. p53 protein expression was found in eight of 17 (47%) samples. Abnormalities in polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis were observed in 16 (94%) samples. A total of 14 missense mutations were detected in eight (47%) samples; 11 were clustered in exon 5 and the remaining three were located in exon 8. UV-like mutations were seen in five of 14 (36%) mutations, but no CC to TT transitions, UV-fingerprint mutations were observed. Multiple mutations were present in two cases and double mutation in a single case. Each lesion in multiple Bowen's disease showed different mutations and was suggested to be of different clonal origins. TP53-loss of heterozygosity (LOH) was detected in four out of 15 (27%) informative samples. Clustering of mutations in exon 5 suggests the role of another carcinogen in Koreans or Asians other than the UVR. Microdissection would increase the detection rate of the p53 gene mutations and LOH not only in skin cancer but also in precancerous lesions.
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PMID:p53 gene mutations in Bowen's disease in Koreans: clustering in exon 5 and multiple mutations. 1094 May 5

The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) has been recently used as a marker of malignancy. This technique was applied to examine 17 skin tissue samples of Bowen's disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen's disease were completely negative. Compatible with this result, the basal cells in Bowen's disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical staining with 34 beta E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14), which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen's disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen's disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 beta B4 (monoclonal antibody against cytokeratin 1), which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen's disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen's disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously. Our findings clearly indicate that the basal cells in Bowen's disease are normal. In support of this conclusion, the same cells showed normal morphology on electron microscopy with preserved basement membrane, although the latter was often damaged in actinic keratosis.
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PMID:Comparative histochemical study of Bowen's disease and actinic keratosis: preserved normal basal cells in Bowen's disease. 1151 39

Actinic keratoses (AK) and Bowen's disease (BD), both intraepidermal skin tumors, have a potential progression to squamous cell carcinoma (SCC). To evaluate the malignant potential of AK and BD, the expression pattern of p53 protein and proliferating cell nuclear antigen (PCNA) were examined in five types of AK and BD by immunohistochemistry. The ultrastructural difference of epidermal cells between AK and BD lesions was investigated. In the study of p53 and PCNA expression, the atrophic and acantholytic types of AK showed lower positive rates compared to others. These two types did not demonstrate all layers expression pattern. The number of desmosomes of the epidermal cells was significantly reduced in BD, and in the bowenoid and hypertrophic types of AK compared with other types of AK The number of hemi-desmosomes showed greatest reduction in BD and the bowenoid type of AK On the basis of our findings, it is hypothesized that atrophic and acantholytic types of AK may have the lowest, and the bowenoid type of AK and BD may have the highest, malignant potential.
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PMID:An assessment of the malignant potential of actinic keratoses and Bowen's disease: p53 and PCNA expression pattern correlate with the number of desmosomes. 1239 64

We examined the presence of human papillomavirus (HPV) DNA in tissues of premalignant skin lesions, i.e., actinic keratosis (n = 13) and Bowen's disease (n = 62), taken from 69 Japanese immunocompetent and renal transplant recipient patients. Detection and typing of HPV DNA were performed using polymerase chain reaction (PCR) and sequence analysis or restriction fragment length polymorphism (RFLP) analysis, respectively. The positivity rates of HPV DNA in tissues of actinic keratosis and Bowen's disease were 77% and 65%, respectively. Twenty-seven HPV types were detected in 50 (67%) premalignant skin lesions, in which Z95963 (accession no. in the EMBL Databank), Z95968, AJ010823, and AJ000151 have been described as partial sequences of unknown HPV types. Furthermore, 2 unknown types, HPVX1 and HPVX2, were found in specimens of actinic keratosis. Sequence analysis showed that HPVX1 is related to HPV-37 (86.1% sequence homology) and that HPVX2 is related to HPV-38 (79.7%). These results indicate that various mucosal and epidermodysplasia verruciformis-related HPV types are associated with the pathogenesis of actinic keratosis and Bowen's disease. In addition, 24 specimens of HPV-positive or HPV-negative premalignant skin lesions were examined immunohistochemically for proliferating cells to determine biological differences between HPV-positive and HPV-negative lesions. Immunohistochemistry for p21(Waf1/Cip1), p53, proliferating cell nuclear antigen (PCNA), Ki-67, and Bcl-2 revealed that there was no significant difference in the cell proliferation activity between HPV-positive and HPV-negative lesions, suggesting that HPV infection alone does not induce cell proliferation in those lesions.
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PMID:Human papillomavirus infection in actinic keratosis and bowen's disease: comparative study with expression of cell-cycle regulatory proteins p21(Waf1/Cip1), p53, PCNA, Ki-67, and Bcl-2 in positive and negative lesions. 1456 84

Post-transcriptional modification of p53 by phosphorylation has been proposed as an important mechanism of p53 stabilization and functional regulation. However, little is known about the phosphorylation state of mutant p53 protein overexpressed in human tumors. We evaluated immunohistochemically the p53 phosphorylation state of Ser392 and Ser15 sites in 44 actinic keratoses (AKs), 62 squamous cell carcinomas (SCCs), 23 Bowen's disease (BDs) and 43 basal cell carcinomas (BCCs). The mean labeling index (LI) of phospho-Ser392-p53 was significantly higher than that of phospho-Ser15-p53 in all cases. Phospho-Ser392-p53 protein was frequently overexpressed in not only SCCs but also AKs and BDs, revealing no significant difference in the immunoreactivity among them. In BCCs, phospho-Ser392-p53 immunoreactivity was significantly lower than that in BDs, and phospho-Ser15-p53 immunoreactivity was significantly lower than that in SCCs. Ser15 phosphorylation was significantly correlated with a high level of Ki-67 LI in BCCs. These results suggest that p53 overexpressed in skin tumors is more frequently phosphorylated at Ser392 residue than Ser15, and that the Ser392 phosphorylation is more likely to occur early in the pathogenesis of SCC. Moreover, the decreased level of the phosphorylation might be characteristic of BCC, but the Ser15 phosphorylation seems to have an influence on BCC development.
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PMID:Phosphorylation state of tumor-suppressor gene p53 product overexpressed in skin tumors. 1549 90

Actinic keratosis (AK) is a common sun-induced precancerous neoplasm confined to the epidermis. The AK is the initial manifestation of a continuum of clinical and histologic abnormalities that progresses to invasive squamous cell carcinoma (SCC). Bowen's disease, also known as squamous cell carcinoma in situ, represents early SCC confined to the epidermis. More than half of all SCCs contain p53 tumor suppressor gene mutations. Like SCCs, the vast majority of AKs and Bowen's disease lesions are asymptomatic. Each AK and suspicious lesion should be treated before it progresses to invasive SCC. Destructive modalities, such as cryosurgery using liquid nitrogen and electrodesiccation and curettage, usually performed by a dermatologist, are the mainstays of therapy.
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PMID:Premalignant and early squamous cell carcinoma. 1581 19

Here we report a case of myelodysplastic syndrome (MDS) with myelofibrosis associated with Bowen's disease. A female patient had undergone an operation and chemotherapy for ovarian cancer when she was 65 years old, and she developed MDS at the age of 70 years old. PCR-single strand conformation polymorphism (SSCP) analysis of peripheral blood mononuclear cells, a Bowen's disease lesion, and normal skin showed an abnormal peak in TP53 exon5. Direct sequencing revealed that they all had missense mutation in codon 175 (G to A) of arginine switched to histidine, suggesting a germline mutation of TP53. It was speculated that p53 function was lost by TP53 germline mutation with the loss of a wild type allele induced by the chemotherapy against ovarian cancer, leading to the development of MDS. No therapeutic effects of low dose melphalan or cyclosporine A on MDS were observed, however one month of 30 mg/day prednisolone administration induced a hematological response.
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PMID:A patient with TP53 germline mutation developed Bowen's disease and myelodysplastic syndrome with myelofibrosis after chemotherapy against ovarian cancer. 1594 83

Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various cancers, including experimentally promoted tumors, gastrointestinal cancers, breast tumors and skin tumors. The mechanism that controls COX-2 expression is not yet clear. Currently, it is reported that COX-2 expression is frequently associated with mutated p53 genes. The goal of this study was to evaluate the expression patterns of COX-2 and p53 in several skin tumors and their correlation. An immunohistochemical method was used to investigate the expression of COX-2 and p53 proteins on formalin-fixed, paraffin-embedded tissue specimens of squamous cell carcinomas (SCC), basal cell carcinomas (BCC), Bowen's disease (BD), actinic keratosis (AK) and porokeratosis. The expression of COX-2 increased in 50% (5/10) of SCC, 80% (8/10) of BCC, 40% (4/10) of BD, 50% (5/10) of AK, and 20% (2/10) of porokeratosis cases. The expression of p53 increased in 90% (9/10) of SCC, 70% (7/10) of BCC, 70% (7/10) of BD, 50% (5/10) of AK, and 40% (4/10) of porokeratosis cases. COX-2 positivity rates of the p53-positive skin tumors were 56%, 100%, 57%, 80% and 25% in SCC, BCC, BD, AK and porokeratosis, respectively. However, the correlation between p53 and COX-2 expression in skin tumors was not statistically significant (P > 0.05). Our results indicate that skin COX-2 and p53 may play roles in skin tumors, but that there is no apparent correlation between the two markers.
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PMID:Immunohistochemical study of cyclooxygenase-2 and p53 expression in skin tumors. 1670 Jun 63

Chronic arsenic poisoning is a world public health issue. Long-term exposure to inorganic arsenic (As) from drinking water has been documented to induce cancers in lung, urinary bladder, kidney, liver and skin in a dose-response relationship. Oxidative stress, chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis. Arsenic tends to accumulate in the skin. Skin hyperpigmentation and hyperkeratosis have long been known to be the hallmark signs of chronic As exposure. There are significant associations between these dermatological lesions and risk of skin cancer. The most common arsenic-induced skin cancers are Bowen's disease (carcinoma in situ), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with As-BD are considered for more aggressive cancer screening in the lung and urinary bladder. As-BD provides an excellent model for studying the early stages of chemical carcinogenesis in human beings. Arsenic exposure is associated with G2/M cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and As-BD lesions. These cellular abnormalities relate to the p53 dysfunction induced by arsenic. The characteristic clinical figures of arsenic-induced skin cancer are: (i) occurrence on sun-protected areas of the body; (ii) multiple and recrudescent lesions. Both As and UVB are able to induce skin cancer. Arsenic treatment enhances the cytotoxicity, mutagenicity and clastogenicity of UV in mammalian cells. Both As and UVB induce apoptosis in keratinocytes by caspase-9 and caspase-8 signaling, respectively. Combined UVB and As treatments resulted in the antiproliferative and proapoptotic effects by stimulating both caspase pathways in the keratinocytes. UVB irradiation inhibited mutant p53 and ki-67 expression, as well as increased in the number of apoptotic cells in As-BD lesions which resulted in an inhibitory effect on proliferation. As-UVB interaction provides a reasonable explanation for the rare occurrences of arsenical cancer in the sun-exposed skin. The multiple and recurrent skin lesions are associated with cellular immune dysfunction in chronic arsenism. A decrease in peripheral CD4+ cells was noticed in the inhabitants of arsenic exposure areas. There was a decrease in the number of Langerhans cells in As-BD lesion which results in an impaired immune function on the lesional sites. Since CD4+ cells are the target cell affected by As, the interaction between CD4+ cells and epidermal keratinocytes under As affection might be closely linked to the pathogenesis of multiple occurrence of arsenic-induced skin cancer. In this review, we provide and discuss the pathomechanisms of arsenic skin cancer and the relationship to its characteristic figures. Such information is critical for understanding the molecular mechanism for arsenic carcinogenesis in other internal organs.
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PMID:Arsenic carcinogenesis in the skin. 1680 64

The aim of our study was to elucidate the characteristics of HPV expression and cell proliferation in actinic keratosis and Bowen's disease of the skin. We examined immunocompetent patients with premalignant lesions of the skin such as actinic keratosis and Bowen's disease. 10 patients were involved in each group. Clinical study included gross features of lesion, growth rate, colour, size. Paraffin sections from biopsy specimens were were stained by hematoxylin-eosin and von Gieson. Immunohistochemistry was performed using monoclonal antibodies against HPV, oncoprotein p53, anti-apoptotic protein Bcl-2, proliferation marker PCNA. Strongly, moderately and weakly positive cells were counted. Actinic keratosis and Bowen's disease failed to show the specific clinical features, therefore, they can not be diagnosed based on clinical signs only and morphological examination seems to be mandatory. The immunohistochemical study has showed that in both actinic keratosis and Bowen's disease HPV was positive in 60%, and 40% were HPV-negative suggesting the similar incidence of HPV infection in these premalignant lesions. Our results suggest that HPV(+)/p53(+) types of actinic keratosis and Bowen's disease are characterized by higher proliferation activity in comparison to HPV(-)/p53(+) types, and expression of Bcl-2 is associated with HPV-negativity, therefore, these premalignant lesions of the skin require immunohistochemical examination with evaluation of expressions of human papillomavirus, proliferation marker PCNA and anti-apoptotic protein Bcl-2. The differential diagnosis of actinic keratosis and Bowen's disease should be based on the following immunohistochemical criteria: incidences of positivity for p53, Bcl-2 and PCNA are similar, but expression intensity and anatomical localization are different: their expressions are higher in Bowen's disease, positive cells are found primarily in upper epidermis in actinic keratosis, while whole epithelium is involved in Bowen's disease.
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PMID:The characteristics of human papillomavirus expression and cell proliferation in actinic keratosis and Bowen's disease of the skin. 1690 62


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