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Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the expression of p53 protein in 28 premalignant and 40 malignant squamous cell proliferations of the larynx and its relationship to tobacco consumption, human papillomavirus infection and differentiation grade of the lesions, p53 expression was examined by means of a microwave post-fixation immunohistochemical method using the PAb 240 and PAb 1801 monoclonal antibodies. HPV infection was assessed by non-isotopic in situ hybridization (NISH) and polymerase chain reaction (PCR). A large proportion of carcinomas (77.5%) and dysplasias (61%) expressed p53. No difference was found between differentiation grades of the lesions regarding p53 detection (P > 0.1), but moderate or intense p53 expression was more frequent in the carcinomas (P < 0.05). A statistical correlation was found between cigarette consumption and both p53 detection and p53 staining intensity (P < 0.05 in each case). HPV study revealed HPV 16 and 18 infection only in carcinomas. The frequency was 28% and the physical state of the virus as demonstrated by NISH was integration into the genome. We observed an inverse relationship between HPV infection and p53 expression (P = 0.006). Our findings suggest that p53 overexpression is a common and early event which increases in frequency with progression of laryngeal squamous cell carcinoma. The expression of p53 is influenced by tobacco and high-risk types of HPV.
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PMID:Expression of p53 protein in laryngeal squamous cell carcinoma and dysplasia: possible correlation with human papillomavirus infection and clinicopathological findings. 785 72

The aims of this study were to determine the incidence of p53 overexpression in squamous cell carcinoma of the larynx and to establish whether or not this bore any relationship to survival, location, stage, histological differentiation, nuclear atypia, mitotic activity, stromal desmoplasia, tumor-associated tissue eosinophilia, or stromal lymphoplasmocytic infiltration. Paraffin blocks from 51 cases of laryngeal squamous cell carcinoma with a minimum follow-up period of 36 months were recut and stained immunohistologically with anti-p53 antibody using the streptavidin-biotin technique. Results were compared with clinicopathological features with Kruskal-Wallis and Mann-Whitney tests. Sixty-three percent of tumors showed positive staining for p53, and in addition, 15% of the sections with adjacent normal or dysplastic mucosa showed positive staining. No relationship between p53 staining and prognosis or any other one of the aforementioned clinicopathological parameters was observed. Although p53 overexpression is a common feature in laryngeal carcinomas, it does not seem to have an impact on prognosis and it does not bear any relationship to the aforementioned clinicopathological parameters.
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PMID:Overexpression of p53 in laryngeal carcinoma: clinicopathological implications. 856 66

Using the monoclonal antibody DO-7, the expressions of P53 protein in 38 cases of laryngeal squamous cell carcinoma (LSCC), and 29 cases of laryngeal benign neoplasms (LBN) were studied immunohistochemically. The results showed that: (1) 25 of 38 (66%) LSCCs, but only 2 of 29 (7%) LBNs showed expression of mutant-type P53 protein. The high rate of P53 protein expression was related to the occurrence of laryngeal carcinoma, and is valuable in diagnosis and differential diagnosis of laryngeal carcinoma; (2) in some LSCCs, the mutant-type P53 protein was also expressed in dysplastic epithelium near the cancer tissues. These epithelial cells near the tumor in which P53 gene has been altered, probably are the source or portent of tumor recurrence; (3) the five year survival rate of mutant-type P53 protein negative LSCC patients was higher than that of positive LSCC patients. The expression of mutant-type P53 protein might be related to LSCC prognosis.
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PMID:[Expression of P53 protein in laryngeal carcinoma and its clinical significance]. 876 27

We performed an immunohistochemical analysis to investigate the expression of p53 protein in a panel of 18 laryngeal squamous cell carcinomas, 15 primary tumours and three in relapse, previously analysed by us for the presence of p53 gene mutations. Dysplastic and/or normal surrounding mucosa was evaluated in 15 different tumours. The results of our study are the following: (1) expression of p53 protein was observed in one out of five tumours positive for p53 gene mutations (20%) and in 10 out of 13 (80%) negative cases; (2), p53 protein over-expression was frequently observed in normal and/or dysplastic mucosa surrounding either wild-type (7/11) or mutated p53 tumours (2/4); (3), p53 immunoreactive cells showed a pattern of distribution in normal and mildly/ moderately dysplastic mucosa (basal layers), different from that in severely dysplastic mucosa (whole thickness). These data further support the hypothesis that p53 protein over-expression may be a marker of the earliest phases of multistep tumorigenesis in laryngeal squamous cell carcinoma.
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PMID:p53 protein expression in laryngeal squamous cell carcinomas bearing wild-type and mutated p53 gene. 880 94

Using polymerase chain reaction (PCR)-SSCP (single-strand conformation polymorphism) and PCR-DNA sequencing analysis, we screened 61 cases of laryngeal squamous cell carcinoma for mutations in exons 5-8 of the p53 gene. Mutations were found in 31.3% (19 of 61) of the laryngeal cancers. Seventeen of 19 (84.2%) cases showing p53 gene mutations were stage III and IV, which suggests that p53 gene mutation is a rather late event in tumor development and is involved in the progression of laryngeal squamous cell carcinoma. A high frequency of G:C to T:A transversion (50%, seven of 14), especially G to T (35.7%, five of 14), was noted in laryngeal carcinoma samples in our study. This finding may point toward an environmental carcinogen (such as tobacco smoke) as an important agent in the genesis of laryngeal squamous cell carcinoma. Most of the p53 gene mutations (18 of 19) found in our studies could change the protein and thus may cause an inactivation of the p53 tumor suppressor gene, strongly suggesting that p53 gene mutation plays a crucial role in the progression of laryngeal carcinoma.
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PMID:Tumor suppressor p53 gene mutation in squamous cell carcinoma of the larynx. 886 34

Chemical influences, mainly heavy tobacco smoking, chewing snuff, excessive alcohol consumption, and some occupational hazards, are known to be important etiologic factors in laryngeal carcinogenesis. The synergistic or cooperative interaction of human papilloma virus (HPV) infection with these chemical factors are serious considerations in the development of laryngeal carcinoma. With the development during the last decade of Southern blot hybridization and polymerase chain reaction (PCR), extensive and comprehensive studies have been conducted to determine the presence and biological (etiologic) significance of HPV. Developed cancer, as well as juvenile and adult multiple and single papilloma of the larynx, have been the subject of clinical and molecular-pathological investigation. Our previous study showed that cancer may develop on the basis of leukoplakia and adult-onset papilloma. Extensive kilocytes, an indication of HPV infection, can be seen by histological examination in papillomas and carcinoma. Literary data suggest that in laryngeal squamous cell carcinoma, including varicoses carcinoma, HPV 16, HPV 18, and HPV 33 DNA have been detected. Both in juvenile and adult-onset respiratory papillomatosis, patients could have either HPV type 6 or 11 DNA sequences. Molecular biological and PCR studies indicate that HPV may play an etiologic role in the development of human malignancies of the upper aerodigestive tract and uterine (cervical) origin. However, evidence that unequivocally links HPV infection with laryngeal squamous cell carcinoma is still lacking. In laryngeal cancer, p53 abnormalities are related to smoking-induced mutagenesis rather than HPV. Studies have postulated an interaction between HPV infection and chemical carcinogens and have concluded that HPV possibly are co-adjuvants during the multistage process of neoplastic transformation.
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PMID:Some etio-pathogenetic factors in laryngeal carcinogenesis. 921 6

An organotypic, tridimensional cell culture, also called a raft system, was used to study the influence of fibroblasts on epithelial carcinogenesis in a cell line derived from laryngeal squamous cell carcinoma and harboring a mutated p53. Differences between the effects of normal fibroblasts and those of tumor-derived fibroblasts were compared by means of fibroblasts taken from the normal skin and from the tumor of a cancer patient and cultivated with epithelial carcinoma cells in an organotypic culture. To study cell contact-mediated changes, the fibroblasts were either simply embedded in collagen matrix or additionally brought into direct contact with epithelial cells. Control epithelial cells were cultivated without any fibroblasts in an organotypic model. A protein panel [p53, p21, PCNA, bcl-2, Ki67, total cytokeratin (CK), CK 8, CK 10, CK 17, CK 18, CK 19, vimentin] involved in cell cycling and epithelial differentiation was assessed immunocytochemically in all organotypic cultures with fibroblasts, in tumor cells cultivated as a monolayer, and in the original tumor sample. The most dysplastic phenotype was obtained when tumor-derived fibroblasts were used in direct contact with epithelial cells, whereas the most benign phenotype was seen when skin fibroblasts had no contact with them. The intensive staining seen for p53 can be explained by p53 mutations also reflecting the weak expression of p21 and abundant expression of PCNA. The intensive Ki67 staining seen in all sections paralleled that of PCNA and marked active cellular proliferation. The CK staining pattern seen in cultured epithelia toward embryonic CKs, CK 8 and CK 18, suggested a simple epithelial phenotype. CK 19 was found only in the epithelium where no direct contacts had occurred. Vimentin expression increased when the raft epithelium was shifting toward a more benign phenotype. The results stress the importance of the origin of fibroblasts as well as the role of direct cellular contacts in modifying the epithelial phenotype even when the epithelial cells are malignant.
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PMID:Fibroblasts can modulate the phenotype of malignant epithelial cells in vitro. 928 67

The present study involves an immunohistochemical analysis of p53 protein expression in head and neck tumours located at two separate subsites, the larynx and hypopharynx. It attempts to relate differences in expression to differences in the behaviour of these tumours. Detection of the p53 protein was performed using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53 overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the laryngeal specimens analysed. Some differences between the two tumour types were noted in the pattern staining. p53 staining in those with hypopharyngeal tumours was associated with a statistically significant increased survival. For laryngeal carcinoma the converse was true but did not reach statistical significance. Differences in the behaviour of different head and neck tumour types may be reflected in differences in expression of the p53 protein. While p53 protein expression does not appear to be a useful prognostic indicator in laryngeal carcinoma it might be a useful prognostic indicator in tumours of the hypopharynx. Moreover, it may help predict those tumours which are radioresistant, thus suggesting other modes of treatment for these tumours. Of particular importance is the molecular basis for the observed differences in survival associated with p53 expression in the two tumour sites. This is under further investigation.
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PMID:p53 protein expression in tumours from head and neck subsites, larynx and hypopharynx, and differences in relationship to survival. 956 67

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.
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PMID:Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination. 981 33

Using immunohistochemical techniques with p53 monoclonal antibody DO-7 and polymerase chain reaction with type specific primers, we detected the expression of p53 of laryngeal and hypopharyngeal squamous cell carcinoma (L-HSCC) in 42 patients, tissues around tumor in 25 patients, human papilloma virus (HPV) 16/18 DNA in paraffinembedded carcinoma tissues from 13 patients with laryngeal squamous cell carcinoma (LSCC). The results showed that overexpression of p53 was detected in 54.8% (23/42) of L-GSCC and 20% (5/25) of hyperlasia epithelia, respectively. There was no correlation of p53 overexpression with clinical stages and histological grading of tumors (P > 0.05). HPV16 DNA encoding E6 protein was detected in 23.1% (3/13) LSCC tissues by PCR. The results suggest that overexpression of p53 and HPV infection are not only associated with pathogenesis of this kind of cancer but also cooperated during carcinogenesis.
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PMID:[A preliminary study on p53 gene expression and infection of human papilloma virus in laryngeal squamous cell carcinoma]. 986 14


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