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)

A critical research frontier in head and neck oncology involves defining the use of induction chemotherapy regimens to allow organ preservation and to avoid functionally debilitating surgical resections. Completed clinical trials in laryngeal cancer indicate that such an approach is feasible, but progress thus far has been limited by our inability to predict which patients are likely to respond to chemotherapy and preserve their larynx. Mutation of the p53 tumor-suppressor gene is the most common genetic alteration identified thus far in human cancers, and it may be important in regulation of cell proliferation and chemosensitivity. To determine whether p53 overexpression predicts chemotherapy response, organ preservation, and survival in patients with advanced laryngeal cancer, we analyzed immunohistologic expression of p53 in tissue sections from 178 patients with advanced laryngeal cancer who were entered in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multiinstitutional clinical trial comparing induction chemotherapy (cis-platinum and 5-fluorouracil) plus radiation therapy (94 patients) to surgery plus postoperative radiation therapy (84 patients). Larynx preservation was significantly higher in the group of patients whose tumors overexpressed p53 (74% vs. 52.5%; p = 0.03). The presence of p53 overexpression did not predict survival in either the surgery or the chemotherapy groups (p = 0.82 and p = 0.53).
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PMID:Overexpression of p53 predicts organ preservation using induction chemotherapy and radiation in patients with advanced laryngeal cancer. Department of Veterans Affairs Laryngeal Cancer Study Group. 756 13

Biopsies from 34 patients with cancer of the head, neck or esophagus, 2 laryngeal papillomas, and 2 normal tonsils were analysed for human papillomavirus (HPV), Epstein Barr virus (EBV) genomes and mutated or elevated levels of p53. In 4 biopsies p53 was also analysed by DNA sequencing. HPV type 31 was found in one laryngeal cancer with normal p53 and HPV type 16 in two tonsil cancers with aberrant p53 expression. EBV was detected by PCR in 11 biopsies, but in situ hybridisation and immunohistochemistry, did not confirm this finding. Aberrant p53 expression was observed in approximately half of the tumours. These results support the involvement of both aberrant p53 expression and HPV in the aetiology of squamous cell carcinoma of the head and neck.
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PMID:Involvement of aberrant p53 expression and human papillomavirus in carcinoma of the head, neck and esophagus. 806 97

We performed a retrospective, longitudinal study to determine whether abnormalities in immunohistochemical staining for the epidermal growth factor receptor (EGFR), p53, or cyclin D1 occur before the development of laryngeal carcinoma. Staining was performed on 63 paraffin-embedded biopsies from 18 patients who subsequently developed carcinoma in situ (CIS) or invasive carcinoma of the larynx. These were compared to 71 biopsies from 20 patients who did not develop CIS/cancer (minimum follow-up period, 4 years). Also studied were the 34 biopsies containing CIS and/or carcinoma from those patients who progressed and 22 biopsies obtained concurrently. The two patient groups did not differ significantly in terms of tobacco and alcohol use. Distinct patterns of staining correlated with malignant progression. These included EGFR staining of two thirds or more of the epithelium thickness, a linear basal p53 staining pattern, and strong (3+) staining for cyclin D1 (P < 0.01 for each). These staining patterns also correlated with increasing atypia. In our study population, linear basal staining for p53 and strong staining for cyclin D1 had higher specificity for progression than did EGFR overexpression, which was also seen in association with inflammation and chronic irritation. Marked site-to-site variation was seen in the immunohistochemical staining and in the degree of atypia, suggesting that multiple biopsies are necessary to properly assess risk. These immunohistochemical staining patterns may be clinically useful to predict patients at risk for neoplastic progression.
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PMID:Immunohistochemical staining for markers of future neoplastic progression in the larynx. 861 72

The incidence of p53 antigen and human papillomavirus (HPV) expression in archival formalin-fixed, paraffin-embedded tissue sections from verrucous carcinoma of the larynx was determined using immunohistochemistry. The p53 oncoprotein was detected in four of 10 tissue samples (40 per cent). The same number of tumours had HPV antigen, and three cases had both p53 oncoprotein and HPV antigen. All positive cases were from heavy smokers and drinkers. After surgical treatment, no tumour recurrence was present in our series. Four patients developed a second head and neck neoplasm and death occurred in three. Three of the patients with second tumour had p53 positive immunoreactivity and two had p53 and HPV expression. Verrucous carcinoma of the larynx presented with overexpression of p53 antigen in a similar percentage to other head and neck cancers. The p53 immunohistochemical determination is well correlated with HPV detection and could have prognostic value in these tumours, but no statistical evidence was present.
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PMID:Human papillomavirus and p53 oncoprotein in verrucous carcinoma of the larynx. 886 7

A comparison was performed of staining intensity of immunohistochemical proliferating antigens (p53, PCNA, Ki67), DNA flow cytometry and ultrastructure of the carcinoma cells in 120 cases of laryngeal cancer. Clinically very advanced tumors were in majority (T3 - 43%, T4 - 18%). A 5 graded scale was adapted to evaluate the level of immunohistochemical staining of the carcinoma cell nuclei. A positive staining was obtained in 70% for p53, 57% for Ki67 and in 80(2/3) for PCNA. 62% of the cases were DNA diploid and 38% DNA aneuploid. The DNA diploid carcinomas were accompanied by the enlargement of the cell nuclei, preserving of the nuclei's wide margins of heterochromatine, enlargement of the nuclear area and increase of the number of nuclei. In the aneuploid-polyploid cancer the nuclei had a substantial polymorphism with large cleaved nuclei and with significant variation in size, and with nuclear envelope. A frequent finding was euchromatization of chromatine. Dense chromatine appeared in the form of small clumps spread over the whole area of these irregular nuclei. Enlargement and activation of nucleoli occurred. There was a positive correlation (Chi-square) between T- and N-stage and immunohistochemical staining. There was also a positive correlation in staining intensity between p53, Ki67 and PCNA. There is also strong correlation between these markers of proliferative activity and the degree of aggressiveness of the tumour.
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PMID:[Diagnostic and prognostic value of p53 oncogene and the selected neoplastic markers (Ki67, PCNA, DNA ploidy) of the ultrastructure in patients with laryngeal cancer]. 917 91

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

The MDM-2 gene encodes for a nuclear phosphoprotein that binds p53 and inhibits its ability to activate transcription by concealing the p53 activation domain. It has been suggested that MDM-2 overexpression might represent an alternative mechanism by which p53-mediated pathways are inactivated in human tumors. MDM-2 overexpression can be detected by immunohistochemical analysis as a result of gene amplification and/or increased mRNA expression. We studied MDM-2 gene amplification and protein overexpression in 46 and 50 cases, respectively, of laryngeal squamous cell carcinomas previously analyzed for p53 gene alterations. Not one of the cases showed MDM-2 gene amplification, whereas MDM-2 nuclear immunoreactivity was found in 17 tumors (34%). In 10 of these, coexpression of p53 protein was detectable in the absence of gene mutations in exons 5 through 9 (P = .03). Likewise, MDM-2 was also overexpressed in 18 (46%) of 39 morphologically normal mucosa samples, 15 (50%) of 30 preneoplastic lesions, and 9 (40%) of 22 cases of severe dysplasia. Finally, we found no significant correlations between MDM-2 expression (neither per se nor in association with wild-type or mutated p53), and the evaluated clinicopathologic parameters of histologic grade, lymph node status, or clinical stage. Our results suggest that MDM-2 gene amplification might not occur in laryngeal carcinomas and that MDM-2 protein overexpression might represent an alternative mechanism by which p53 is inactivated in the early stages of laryngeal cancer tumorigenesis.
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PMID:MDM-2 oncoprotein overexpression in laryngeal squamous cell carcinoma: association with wild-type p53 accumulation. 926 20

Matrix metalloproteinases are believed to play an important role in tumor progression, invasion and metastasis. In order to investigate if the expression of stromelysin-3 (ST3) mRNA could add prognostic information concerning invasive laryngeal cancer and/or be indicative of a high risk for tumor progression in laryngeal dysplasias ST3 expression was analyzed by in situ hybridisation of formalin fixed paraffin embedded laryngeal specimens. Furthermore, all specimens underwent image cytometry (ICM) DNA analysis, and, p53 immunostaining. Invasive epithelial cancer, both localized (T1, T2) cancers, cured, as well as not cured, by radiotherapy, and cases with regional lymph node metastases were studied. Furthermore, high grade and low grade dysplasias, selected for rapid, slow and non-progression, as well as non-neoplastic inflammatory lesions were investigated. Expression of the ST3 gene was found in 9 out of 14 (64%) invasive cancer lesions, and in 3 out of 10 (30%) dysplasias, thus indicating that ST3 expression correlates to tumor progression. The ST3 positive laryngeal cancer lesions displayed a higher degree of DNA aberration than the ST3 negative lesions thus suggesting that ST3 positivity could indicate highly malignant tumors. Of the three ST3 positive dysplasias, the first progressed rapidly to cancer in situ with suspected microinvasion. The second ST3 positive dysplasia progressed to invasive cancer within five months. The third ST3 positive dysplasia had been radically excised and hereby cured. All but one of the dysplastic lesions showed p53 immunoreactivity, and all dysplasias exhibited aneuploid cells. ST3 expression appears to be a late event in the multistage process of carcinogenesis and could prove useful as an indicator of dysplasias with imminent risk for progression to invasive cancer.
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PMID:Stromelysin-3 mRNA expression in dysplasias and invasive epithelial cancer of the larynx. 949 47

To evaluate the predictive role of the oncogenes p53, MDM-2 and cyclin D1, and the proliferative marker Ki67, in the progression from low-grade dysplasia to carcinoma of the larynx. We studied immunohistochemically a series of 32 low-grade pre-neoplastic laryngeal lesions, 10 of which progressed to invasive carcinoma. Immunoreactivity in more than 10 per cent of the dysplastic cells was detected in five cases immunostained with anti-p53 (approximately 15 per cent), in two with anti-MDM-2 (approximately six per cent), and 11 with anti-Ki67 antibodies (approximately 34 per cent), whereas none of the cases showed cyclin D1 overexpression. No significant association was found between p53 and MDM-2 immunoreactivity and the evolution to carcinoma; on the contrary, Ki67 expression was detectable in all but one of the 10 cases developing an infiltrative tumour (90 per cent), and in two of the 22 cases that did not progress (approximately nine per cent) (p = 0.01). These findings indicate that immunohistochemical assessment of the proliferative index in bioptic samples of dysplastic laryngeal mucosa may be useful in selecting patients who should undergo a more specific follow-up evaluation.
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PMID:The predictive value of p53, MDM-2, cyclin D1 and Ki67 in the progression from low-grade dysplasia towards carcinoma of the larynx. 974 74

Tumours of head and neck belong to the most frequent types of cancer world-wide. In Poland, mortality from larynx cancer among males has been continuously increasing during the last decades up to 8.4 deaths per 100,000 men in 1993, which exceeds epidemiological records from other countries. The aetiology of laryngeal cancer is strongly associated with exposure to carcinogens present in tobacco smoke. The review describes a sequence of molecular and cellular events from carcinogenic exposure, DNA adduct formation, detection of mutations in the p53 gene, loss of heterozygosity (LOH) in chromosomal loci encoding the p53 and p16 genes, and loss of control of the cell cycle. The section concerning DNA adducts includes a discussion of the role of such confounders as exogenous exposure, the age and sex of the subject, and disease progression. The significance of genetic factors as individual risk determinants is discussed in relation to bleomycin-induced chromosome instability and in connection with the occurrence of defects in genes encoding detoxifying enzymes. The question concerning the substantial difference between men and women in larynx cancer morbidity and mortality remains open, even when the significantly higher adduct formation in male DNA compared with female material was taken into account. Preliminary experiments suggest a role of the frequently observed loss of the Y-chromosome.
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PMID:Molecular and cellular alterations in tobacco smoke-associated larynx cancer. 1057 35


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