Quantification of p53 in Epithelial Ovarian Cancer

Geisler, John P.; Geisler, Hans; Wiemann, Michael C.; Givens, Stanley S.; Zhou, Zijie; Miller, Greg A.

doi:10.1006/gyno.1997.4799

Cited by 46 publications

(35 citation statements)

References 10 publications

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“…Therefore, diverging results have been reported on the prognostic significance of TP53 alterations in ovarian cancer, especially in early stage. Some studies have shown that TP53 alterations are more frequent in serous adenocarcinoma and in poorly differentiated tumours (Geisler et al, 1997;Leitao et al, 2002;Skirnisdottir et al, 2002), while others were not able to demonstrate these differences (Marks et al, 1991;Fallows et al, 2001;Leitao et al, 2002). Ploidy status has previously been demonstrated to be an independent prognostic factor among earlystage ovarian carcinomas (Vergote et al, 1993;Valverde et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Other clinical, pathological and molecular biological features have therefore been studied in an attempt to identify the additional factors of prognostic importance. Some studies have looked at the prognostic significance of TP53 alteration in ovarian cancers, and addressed the possibility that the clinical behaviour of tumours with TP53 alterations might be significantly different from that of tumours without TP53 alterations (Kohler et al, 1993;Kupryjanczyk et al, 1995;Geisler et al, 1997;Shahin et al, 2000;Fallows et al, 2001;Suzuki et al, 2001;Valverde et al, 2001). However, most of these studies addressed patients with advanced stage of the disease, and analysed relatively small numbers of tumours.…”

Section: Discussionmentioning

confidence: 99%

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TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival

et al. 2004

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We conducted the present study to evaluate the frequency and prognostic importance on long-term survival of TP53 mutations and TP53 protein accumulation in a cohort of 178 patients with early-stage ovarian carcinomas. TP53 mutations scored as aberrant temporal temperature gradient gel electrophoresis pattern from all exons were observed in 39.9% of the tumours. Full screening of exons 5 -8, followed by sequencing, was successful in 135 cases, and 48 mutations altering the protein were detected in 39 cases (28.9%). TP53 mutations were slightly less common in the Federation of Gynecologists and Obstetricians stage IA than in IB/IC (P ¼ 0.05). No significant correlations with histological type, grade of differentiation, DNA ploidy status or age at diagnosis were found. TP53 protein accumulation analysed by immunohistochemistry was found in 32.6% of all tumours, and was a poor predictor of TP53 mutations with 56.4% sensitivity, 77.1% specificity, 50% positive predictive value and 81.3% negative predictive value. Neither TP53 mutations nor TP53 protein accumulation influenced the prognosis significantly in this group of patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival

et al. 2004

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“…Nevertheless, several studies (e.g., Agnati et al 1984;PerettiRenucci et al 1991;Cowen and Thrasivoulou 1992;Dobado-Berrios et al 1992;Thal et al 1995) have shown that (semi)quantitative analyses of immunocytochemical preparations provide valid results if the immunochemical and image analytical parameters are vigorously controlled. Such quantifications may even be of diagnostic and prognostic value in clinical appli- cations (e.g., Geisler et al 1997;Kumar-Singh et al 1997;Lehr et al 1997). …”

Section: Discussionmentioning

confidence: 99%

A Semiquantitative Image-analytical Method for the Recording of Dose-Response Curves in Immunocytochemical Preparations

Wicht

Maronde

Olcese

et al. 1999

J Histochem Cytochem.

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SUMMARY Knowledge about intracellular signal transduction cascades is largely based on investigations of cultured cells whose responses to different stimuli are typically quantified via RIA, ELISA, or immunoblots. These techniques, which require relatively large amounts of biological material, are performed with homogenized cells and therefore do not allow localization of the molecules under investigation. We describe a protocol for recording dose-response curves directly from immunocytochemical preparations using rat pinealocytes as a model system. The cells were exposed to ␤-adrenergic stimuli inducing the phosphorylation of the transcription factor CREB (mediated by PKA), an increase in ICER protein levels, and synthesis and release of melatonin. Melatonin concentrations were determined by ELISA. cPKA, phosphorylated CREB, and ICER were demonstrated by immunocytochemistry and immunoblots. Dose-response curves were recorded by measuring the integrated density of the immunoreactive sites with an image analysis program. Dose-response curves from immunoblots and immunocytochemical preparations showed almost identical dynamics, validating the immunocytochemical approach, which minimizes the amount of biological material needed for such studies, allows combined quantification and localization of biomolecules, and may even be more sensitive than immunoblotting.

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“…These factors seem to interact at the molecular level (9,10,14,15). Furthermore, there is a growing body of literature that suggests that these factors modify clinical outcome in several cancers (21, 22, 30, 38 -40), including advanced epithelial ovarian cancer (9,16,26). Thus, it is rational to suspect that these factors may also contribute to the outcome of stage I ovarian cancers.…”

Section: Discussionmentioning

confidence: 99%

The Relationship of Molecular Markers of p53 Function and Angiogenesis to Prognosis of Stage I Epithelial Ovarian Cancer

Goodheart

Ritchie

Rose

et al. 2005

Clinical Cancer Research

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Purpose: Multiple angiogenic factors may influence tumor progression and metastasis. Several are modified by the p53 gene. We sought to identify molecular markers for high-risk stage I epithelial ovarian cancers. Experimental Design: Seventy-seven consecutive stage I epithelial ovarian cancers were evaluated for p53, CD31 microvessel density, thrombospondin-1, vascular endothelial growth factor (VEGF), p21 immunohistochemical staining, and p53 gene mutations. Molecular marker impact upon disease-specific survival, disease recurrence, and distant recurrence was evaluated with Cox regression. Results:There were 12 deaths from disease.Twelve of the 77 tumors contained p53 mutationsö 10 missense and 3 null (one tumor had two mutations). Fesddration Internationale des Gynaecologistes et Obstetristes substage (IA/IB versus IC; P < 0.001) and VEGF staining (P = 0.02) were significant in bivariate models with relationship to disease-specific survival. Stage (P = 0.0004), grade (P = 0.008), histology (P = 0.0025), p53 dysfunction (positive stain and/or mutation; P = 0.048), and microvessel density (P = 0.04) were significant in bivariate models with relationship to time to recurrence. In multivariate analyses among stage IC patients, failure to receive chemotherapy and microvessel density were associated with disease-specific survival, time to recurrence, and time to distant recurrence with hazard ratios of 4.8 to 44.1. Conclusions: The p53-dependent molecular markers of angiogenesis are of limited utility in developing a clinical strategy for postoperative management of stage I ovarian carcinoma. Microvessel density impacts survival and metastasis for high-risk stage IC disease. Adjuvant chemotherapy is necessary, but not sufficient, for cure of high-risk stage I epithelial ovarian cancers.

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Quantification of p53 in Epithelial Ovarian Cancer

Cited by 46 publications

References 10 publications

TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival

TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival

A Semiquantitative Image-analytical Method for the Recording of Dose-Response Curves in Immunocytochemical Preparations

The Relationship of Molecular Markers of p53 Function and Angiogenesis to Prognosis of Stage I Epithelial Ovarian Cancer

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