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)

Using monoclonal antibodies, we have identified a series of tumor-associated antigens selectively expressed on tumor subtypes with distinct clinical behaviours. The mucinous antigen M344 and the gp200 surface antigen 19A211 are preferentially expressed on papillary superficial tumors and carcinoma in situ lesions of the bladder. The combination of these two antigenic markers in immunocytology and flow cytometry studies of exfoliated cells has improved the sensitivity of detection for bladder tumors. Moreover, the detection of M344- and 19A211-positive exfoliated cells from previously treated but currently tumor-free patients appears to be predictive of tumor recurrence on follow-up. These results, as well as results of bladder mapping studies in tumor patients, suggest that these antigenic changes occur in a premalignant stage and may provide tools to monitor the efficacy of chemopreventive measures. Other markers, such as the surface antigen T138 and the soluble molecules autocrine motility factor (AMF) and tumor collagenase stimulating factor (TCSF), are produced by primary or recurrent tumors with a higher metastatic potential. They may be useful in identifying high risk patients for distant failure. The highly restricted antigen 19A211 is also expressed on cervix condylomas and carcinoma. This observation led us to investigate a possible viral etiology of some bladder cancers. Using PCR techniques, we detected the presence of human papillomavirus (HPV) 16 DNA sequences in a significant proportion of bladder tumors. HPV positivity was inversely correlated with the presence of p53 mutations in exons 5-9 of the same tumors as measured by PCR-SSCP technique. This combination of markers may provide a basis for chemoprevention strategies targeted to distinct etiological events.
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PMID:Strategies of chemoprevention based on antigenic and molecular markers of early and premalignant lesions of the bladder. 130 95

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. These changes include activation of dominant oncogenes myc family, (K-ras and neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and RB as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, such studies have not been performed to date. Documentation of molecular changes in premalignant lesions and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.
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PMID:The molecular biology of lung cancer. 130 9

Recognition of premalignant lesions in the oral epithelium has the potential to increase survival rates for squamous cell carcinoma of the oral cavity. It has previously been reported that cytokeratin 19 (CK19), a 40-kd epithelial cytoskeletal protein within the suprabasal squamous epithelium, is a specific marker of moderate-to-severe dysplasia and carcinoma in situ in oral cavity squamous epithelium. In contrast, normal epithelium and hyperplastic lesions reportedly express CK19 only in the basal layer if at all. The authors chose to test and extend this hypothesis by studying suprabasal CK19 expression and dysplasia of the oral cavity and upper aerodigestive tract in paraffin-embedded specimens that had been fixed in alcohol, a superior fixative for the preservation of cytokeratins. The authors examined 56 alcohol-fixed, paraffin-embedded specimens including 37 from the oral cavity, using two antibodies specific for CK19 (Ks19.1 and 4.62), an antibody to the nuclear proliferation marker, proliferating cell nuclear antigen (PCNA) (19A2), and an antibody to the putative tumor suppressor gene, p53 (pAb1801). The lesions were classified as normal, hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia/carcinoma in situ, or invasive squamous cell carcinoma, following standard histologic criteria. Immunocytochemically stained sections were scored for the presence or absence of suprabasal CK19, suprabasal PCNA, and p53 positivity, regardless of location. The immunostaining patterns of the two anti-CK19 antibodies were essentially equivalent. Except for one laryngeal specimen, normal epithelium, when positive, showed CK19 expression only in scattered cells throughout the basal layer. Proliferating cell nuclear antigen-positive nuclei were found exclusively in the basal layer. In areas of hyperplasia, CK19 immunostaining was absent or confined to the basal layer in 20 of 38 specimens and was expressed in suprabasal cells in 18 of 38 hyperplastic specimens. Proliferating cell nuclear antigen immunostaining in all cases of hyperplasia was limited to the basal layer. Severe dysplasia and carcinoma in situ showed suprabasal CK19 staining in six of nine specimens and no CK19 staining in three of nine specimens. In contrast, suprabasal PCNA immunostaining was found in all dysplasia and carcinoma in situ cases. p53 expression was detected in three of nine severe dysplasia/CIS specimens and was immunocytochemically undetectable in all normal, hyperplasia, and mild to moderate dysplasia specimens. The authors conclude that suprabasal CK19 expression is neither a sensitive nor a specific marker of premalignancy in oral epithelium and cannot be used to distinguish hyperplasia from dysplasia. In contrast, a strong correlation between suprabasal expression of PCNA, a marker for proliferating cells, and dysplasia/carcinoma in situ was evident.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Markers for dysplasia of the upper aerodigestive tract. Suprabasal expression of PCNA, p53, and CK19 in alcohol-fixed, embedded tissue. 138 38

The p53 gene is a tumor suppressor gene located on chromosome 17p. Deletions of this chromosome and point mutations of p53 have been implicated in the development of colonic neoplasms. We have analyzed the loss of heterozygosity of the human p53 tumor suppressor gene in 40 cases of colorectal carcinoma using two restriction fragment length polymorphisms detected by BglII and AccII restriction enzymes. p53 gene product expression was studied immunohistochemically in 64 colorectal carcinomas, 18 adenomas, and 40 normal colonic mucosae using an anti-human p53 monoclonal antibody (Pab 1801) and the avidin-biotin-peroxidase complex technique. Twelve of the 40 patients (30%) were polymorphic for the p53 gene. In ten of these informative patients (83%), the tumor samples showed the loss of one allele when compared with normal colorectal samples of the same patient. One of the homozygous patients showed a loss of both p53 alleles. p53 immunostaining was observed in 43 of 64 carcinomas (67%) but only in two adenomas (11%). These two positive adenomas showed areas of carcinoma in situ. The normal mucosa was always negative. No relation could be found between p53 immunostaining and the degree of differentiation, the extension of the tumor, or the Ki-67 proliferative index. Mucinous carcinomas and right-side carcinomas were less p53 immunoreactive (25% and 52%, respectively) than the usual adenocarcinomas (73%) and distal tumors (72%). These findings suggest that p53 may be a target of chromosome 17 deletions and that this gene may play a role in the malignant transformation of adenomas. BglII and AccII restriction fragment length polymorphism analysis of the p53 gene may be a useful and direct technique to detect allelic loss of this gene in tumors.
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PMID:Loss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas. 186 64

Mutations of the p53 gene are important mechanisms in malignant transformation and are associated with dysregulation of normal cell growth. In the present study the expression of mutated p53-protein and proliferating cell nuclear antigen (PCNA) was investigated in a series of 31 human transitional cell carcinomas (TCC) by immunohistochemistry (IHC). The number of PCNA-positive cells and the pattern of expression was distinct in normal urothelium being confined to the basal cell layer. In dysplastic urothelium and in Carcinoma in situ (CIS) PCNA-immunoreactive nuclei were irregularly distributed throughout all layers. In tumor cell complexes the pattern of PCNA-immunoreactivity was different in papillary and primary infiltrating TCCs. Densitometric quantification of the intensity of the PCNA-reactivity using image analysis revealed an increase from normal to dysplastic urothelium and from dysplastic urothelium to invasive tumors. 21/31 (68%) of the tumors and tumor-associated CIS showed overexpression of p53 varying in percentage, pattern and reaction intensity. The percentage of PCNA-positive cells was higher in tumors overexpressing p53. Double IHC showed colocalization of both molecules in a significant proportion of tumor cells suggesting a link of p53 overexpression and the abnormal proliferative activity. The present results show that p53 over-expression is found in a significant percentage of TCCs and indicate a close association with a defective growth regulation resulting in increased PCNA-levels and enhanced cellular proliferation.
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PMID:[Proliferative activity and p53 expression in transitional cell carcinoma of the urinary bladder]. 751 Dec 89

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study. 755 63

Functional disturbance of p53 tumor suppressor protein contributes to uncontrolled cell growth. Human papillomavirus (HPV) E6 oncoproteins bind to wild-type p53 and abrogate its function. Our objective was to elucidate the relation of aberrant p53 protein expression to HPV DNA and cellular atypia in male genital warts and premalignant lesions. Immunohistochemically detectable p53 protein expression was studied in 35 male anogenital warts with low-level or no keratinocyte atypia (histologically confirmed condylomata acuminata), in 25 lesions with bowenoid papulosis (BP; carcinoma in situ) histology, and in 10 non-condyloma lesions using immunostaining with three established antibodies recognizing full-length wild-type accumulated p53 protein, or its conformational mutants. HPV DNA specific for HPV 6/11, 16/18, or 31/33/35 was identified by in situ hybridization or by polymerase chain reaction (PCR) - based amplification. Both nuclear and cytoplasmic keratinocyte immunostaining for p53 protein was detected in 41% of condylomata with no keratinocyte atypia and in 42% of condylomata with slight nuclear atypia or with bowenoid papulosis histology. No association of aberrant p53 expression with any specific HPV type or with HPV DNA was observed. Normal skin and some other penile dermatoses were negative for p53 immunostaining. In the follow-up biopsies of 16 BP patients, treated with CO2 laser, recurrence of atypia was seen exclusively in lesions initially positive for both HPV DNA and p53 protein. Our results show that a few cells in male genital warts even with no cellular atypia may express abnormally sequestered or loss-of-function p53 protein, and that concomitant presence of any type of HPV DNA is associated with recurrencies or progression of premalignant changes.
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PMID:Relation of p53 tumor suppressor protein expression to human papillomavirus (HPV) DNA and to cellular atypia in male genital warts and in premalignant lesions. 765 76

The progression of carcinoma in situ of the bladder to invasive bladder carcinoma has been shown to be essentially regulated by p53 overexpression. In another study, however, loss of heterozygosity of chromosome 9 has also been shown to be essential for progression to muscle invasive disease. Routine random biopsies for predicting prognosis and deciding on adjuvant intravesical therapy should be abandoned because of the results of a well-designed trial on 1745 patients. The aforementioned study showed that the recurrence and progression rates could be only slightly improved at a cost of more intravesical therapy if random biopsies were done routinely. The survival of patients undergoing radical cystectomy was shown to be strongly affected by the primary tumor stage even in those patients with positive nodes. Radical cystectomy and lymph node dissection alone could be beneficial in node-positive patients if the tumor was confined to the bladder. Neoadjuvant chemotherapy and bladder sparing could be recommended only on selected patients with significant reduction in tumor size after chemotherapy. The response to adjuvant chemotherapy could be prolonged if consolidation surgical intervention is performed on responders. With the help of new prognostic parameters obtained from molecular genetic analysis, the already increasing survival trends in bladder carcinomas will hopefully continue to improve in the near future.
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PMID:Recent studies in bladder cancer. 765 32

Frequent recurrences and multicentricity of bladder cancer suggest that alterations of the urothelium distant from the tumor may be relevant to prognosis. In this study immunohistochemistry and fluorescence in situ hybridization (FISH) were used to examine expression of p53, erbB-2, and epidermal growth factor receptor (EGF-r), genomic aberrations, and tumor cell proliferation (Ki67 LI) in normal and dysplastic urothelium. Biopsy specimens examined included normal urothelium (n = 40), mild dysplasia (n = 34), moderate dysplasia (n = 18) and carcinoma in situ (CIS; n = 20). Several different oncogene expression patterns were found, only some of which were associated with dysplasia. EGF-r expression was equally frequent in normal and dysplastic urothelium and showed a strong association with Ki67 LI (P < .0001). A purely superficial erbB-2 positivity was present in both normal and dysplastic biopsies. However, diffuse erbB-2 positivity and p53 overexpression were both associated with advanced dysplasia (P < .0001 each). FISH analysis showed erbB-2 gene amplification and p53 deletions in selected CIS, as well as a marked chromosome 17 copy number heterogeneity in all six CIS examined. These findings indicate a considerable genomic instability in bladder CIS. They show that both erbB-2 and p53 are altered during malignant transformation. Detectable oncogene expression alone, however, is not diagnostic of malignancy in bladder urothelium.
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PMID:Patterns of p53, erbB-2, and EGF-r expression in premalignant lesions of the urinary bladder. 767 97

Carcinoma in situ (CIS) is regarded as the precursor lesion of testicular germ cell tumors. In adults CIS cells have also been described within the normal testicular tissue adjacent to mature teratomas with a frequency of 52-88%. These CIS-cells can be identified by immunohistochemical staining for "placental like alkaline phosphatase" (PLAP). In four of eight patients with mature teratomas CIS was identified by immunohistochemistry for "PLAP" in atrophic testicular tubules adjacent to the tumors. In three of these patients cells of CIS were positive for the p53 oncoprotein, indicating a mutational inactivation of the p53 tumor suppressor gene. The malignant potential of mature teratomas, which do occur without histological signs of malignancy, may therefore be associated with the occurrence of CIS within the histologically normal appearing testicular tissue adjacent to the mature tumor. Immunohistochemical positivity for the p53 protein in CIS cells of some patients may indicate that the mutational inactivation of the p53 tumor suppressor gene could be involved early in the development of testicular germ cell tumors.
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PMID:Overexpression of the p53 oncoprotein in carcinoma in situ of the testis. 774 46


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