Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas

Hagel, Christine; Laking, George; Laas, R.; Scheil, Stefanie; Jung, Roman; Milde‐Langosch, Karin; Stavrou, D.K.

doi:10.1016/s0959-8049(96)00259-6

Cited by 30 publications

(30 citation statements)

References 13 publications

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“…CYP1B1 can convert polycyclic hydrocarbons to diols and epoxides, which interact with DNA, forming stable adducts and single-strand breaks, and have been implicated in the induction of mutations in the p53 gene (22). This is consistent with previous work showing that p53 mutations are prevalent in glioblastomas (23) and oligodendrogliomas (24,25). Previous studies have also shown that p53 mutations and chromosome 1p/19q loss are mutually exclusive within both astrocytomas and oligodendrogliomas (26).…”

Section: Discussionsupporting

confidence: 89%

Cytochrome P450 1B1 Expression in Glial Cell Tumors: An Immunotherapeutic Target

Barnett

Urbauer

Murray

et al. 2007

Clinical Cancer Research

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Purpose: Among central nervous system malignancies, cytochrome P450 1B1 (CYP1B1) expression has only been characterized in medulloblastoma. An immunotherapeutic agent targeting this antigen was shown to safely stimulate a good immune response. To evaluate the viability of further research efforts targeting this antigen, we examined the expression of CYP1B1 in glial cell malignancies. Experimental Design: We studied the frequency and extent of CYP1B1expression by immunohistochemical analysis in 269 glial tumors (including all major pathologic types) on a tissue microarray. Results were categorized by percentage of cells stained and intensity of cytoplasmic staining within cells. Correlation of CYP1B1 expression with patient prognosis was evaluated by univariate and multivariate analyses. Results: Overall, increased CYP1B1 expression in glial tumors was associated with decreased patient survival time (P < 0.0014 for both percentage and intensity of staining). A significant difference existed in percentage and intensity of staining between astrocytic and oligodendroglial tumors (P = 0.0002 and 0.0003, respectively), between grades of tumors (P < 0.0001 and 0.0079), and between pathologic types of tumors (P < 0.0001 and 0.0339). Positive CYP1B1 staining was seen in 81% of glioblastomas, 84% of anaplastic astrocytomas, 61% of oligodendrogliomas, and 67% of anaplastic oligodendrogliomas. Paradoxically, within specific tumor pathologies, there was a trend toward increased survival as CYP1B1expression increased. However, in the multivariate analysis, this trend disappeared, and CYP1B1 expression seemed prognostically neutral. Conclusion: CYP1B1is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.

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Section: Discussionsupporting

confidence: 89%

Cytochrome P450 1B1 Expression in Glial Cell Tumors: An Immunotherapeutic Target

Barnett

Urbauer

Murray

et al. 2007

Clinical Cancer Research

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“…17 Nevertheless, the demonstration of p53 protein accumulation by immunohistochemistry alone has been shown to be of prognostic significance at other sites and may reflect the clinical course of the tumor better than the mere presence of p53 mutations. 3,8,18 To our knowledge to date, the correlation between the occurrence of p53 alterations and poor prognosis in patients with HNSCC remains a matter of debate. Indeed, overexpression of p53 has been related to a worse prognosis in HNSCC, 5,8 although this result still is controversial, and many studies did not report any significant correlation between p53 expression and the prognosis of patients with HNSCC or the clinicopathologic characteristics of the tumor, such as tumor stage, grade of differentiation, invasiveness, lymph node involvement, or distant metastases.…”

Section: Discussionmentioning

confidence: 99%

P53 expression in squamous cell carcinomas of the supraglottic larynx and its lymph node metastases

Cabanillas

Rodrigo

Astudillo

et al. 2007

Cancer

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BACKGROUND.Although p53 overexpression is frequent in head and neck squamous cell carcinomas (HNSCCs), controversy remains regarding the prognostic significance of that overexpression. The objective of this study was to investigate the expression pattern and prognostic significance of p53 expression in HNSCC of the same location, treated in the same way, and with long‐term follow‐up.METHODS.P53 expression was determined by immunohistochemistry in paraffin‐embedded tissue specimens from 107 consecutive patients (107 primary squamous cell carcinomas of the supraglottic larynx and 46 matched lymph node metastases). All patients underwent surgical resection and bilateral neck dissection.RESULTS.A strong correlation was observed between p53 expression in the primary tumor and in the matched lymph node metastases (P = .0001). P53 overexpression in the lymph nodes was an independent predictor of regional recurrence (P = .027). Likewise, expression of p53 in the lymph nodes correlated significantly with disease‐specific survival (P = .018). Five years after treatment, 70% of patients with p53‐negative, metastatic lymph nodes remained alive, whereas only 30% of patients with p53‐positive lymph nodes remained alive. In multivariate analysis, lymph node status and p53 expression in the lymph nodes remained associated with survival.CONCLUSIONS.The current data suggested that, although p53 overexpression is common in supraglottic carcinomas, its expression in the primary tumor is of limited clinical significance. However, the results supported the role of p53 in the lymph node metastases as an independent predictor of regional failure and a poor prognosis in patients with HNSCC. A prospective trial is indicated to validate these findings. Cancer 2007. © 2007 American Cancer Society.

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“…The sections were dried brie y at 37°C, resuspended in 180 µl ATL digestion buffer provided with the kit, and incubated in the presence of Proteinase K at 55°C for 18 h. Subsequently, 200 µl AL buffer from the kit was added, and the probes were further incubated at 70°C for 10 min, then 200 µl absolute ethanol was added, the probes were vortexed, and the DNA was isolated by use of a DNeasy minicolumn. For polymerase chain reaction ampli cation of exons 5-9 of the p53 gene, 3 to 10 µl of the nal DNA preparation was added to a total volume of 100 µl reaction mixture as described previously (Hagel et al, 1996). The following primer pairs (Mashiyama et al, 1991) were used: for exon 5/6, 5-ACCATGAGCGCTGCTAG AT-39 and 59 -AGTTGCAAACCAGACCT-39 ; for exon 7, 59 -GTGTTATCTCCTAGGTTGGC-39 and 59 -CAAGTG GCTCCTGACCTGGA-39 ; and for exon 8/9, 59 -CCTAT CCTGAGTAGTGGTAA-39 and 59 -CCAAGACTTAGT ACCTGAAG-39 .…”

Section: Polymerase Chain Reaction Ampli Cation and Sequencing Of P53mentioning

confidence: 99%

Cytoplasmic localization of wild-type p53 in glioblastomas correlates with expression of vimentin and glial fibrillary acidic protein

Sembritzki¹

2002

Neuro-Oncology

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except for 1 case. No mutation was detected in p53 exons 5 to 8 in tumors with cytoplasmic p53, suggesting that they express wild-type p53. The data indicate that a cytoplasmic accumulation of wild-type p53 in human primary glioblastomas correlates with a certain intermediate lament protein expression, suggesting that it identi es a certain subset of tumors. Neuro-Oncology 4, 171-178, 2002 (Posted to Neuro-Oncology [serial online], Doc. 01-055, April 10, 2002

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Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas

Cited by 30 publications

References 13 publications

Cytochrome P450 1B1 Expression in Glial Cell Tumors: An Immunotherapeutic Target

Cytochrome P450 1B1 Expression in Glial Cell Tumors: An Immunotherapeutic Target

P53 expression in squamous cell carcinomas of the supraglottic larynx and its lymph node metastases

Cytoplasmic localization of wild-type p53 in glioblastomas correlates with expression of vimentin and glial fibrillary acidic protein

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