p53 Expression in Epithelial Ovarian Neoplasms: Relationship to Clinical and Pathological Parameters, Ki-67 Expression and Flow Cytometry

Henriksen, Rudi; Strang, Peter; Wilander, Erik; Bäckström, Torbjörn; Tribukait, Bernhard; Öberg, Kjell

doi:10.1006/gyno.1994.1138

Cited by 87 publications

(48 citation statements)

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“…p53 expression had also independent value in the multivariate recurrence-free analysis. Similar data have been observed in other studies, where p53-positivity has significantly predicted a poor survival (Henriksen et al, 1994;Klemi et al, 1995;van der Zee et al, 1995;Herod et al, 1996). However, contradictory results have been reported as well (Marks et al, 1991;Kohler et al, 1993a;Levesque et al, 1995).…”

Section: Discussionsupporting

confidence: 91%

p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer

Kosma

Hongxiu

et al. 1999

Br J Cancer

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SummaryThe role and prognostic value of the tumour suppressor p21/WAF1 expression in epithelial ovarian cancer has not yet been defined. Therefore, the expression of p21/WAF1 was assessed immunohistochemically (IHC) in 316 epithelial ovarian malignancies in relation to p53, cell proliferation and patient survival. p21/WAF1 expression was inversely correlated with p53 and cell proliferation. Low p21/WAF1 expression was significantly associated with high grade of the tumour (P = 0.0005), advanced FIGO stage (P = 0.001) and primary residual tumour (P = 0.0001). Low p21/WAF1 expression was a marker of poor overall survival (P = 0.012). Similarly, p53-positivity and high cell proliferative activity were significant predictors of poor survival in univariate analyses. Moreover, the patients with p21-/p53+ tumours had a poorer overall (P < 0.00005) and recurrence-free (P = 0.0005) survival in univariate analyses, and the p21/p53 expression independently predicted tumour recurrence in Cox's multivariate analysis. Our results suggest that p21/WAF1 expression is mostly p53-dependent in epithelial ovarian cancer. High p21/WAF1 expression seems to function as a negative cell cycle regulator and as a marker of favourable disease outcome in epithelial ovarian cancer. In addition, the patients with their tumour expressing no or low p21/WAF1 protein but positive for p53 had a notably higher risk of recurrent disease, implicating that these patients might be more prone to treatment failures.

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Section: Discussionsupporting

confidence: 91%

p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer

Kosma

Hongxiu

et al. 1999

Br J Cancer

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“…A strong inverse correlation was observed between high expression of CDKN1A (p21/WAF-1) in LMP-G1 tumors and high expression of Ki-67 mRNA in G2-G3 carcinomas. Immunohistochemical staining with MAbs is strongly correlated with grade, and high expression of Ki-67 protein has been associated with shorter progression-free survival and OS (Henriksen et al, 1994;Marx et al, 1997;Korkolopoulou et al, 2002). In one study, no appreciable difference was found in the relative intensity of Ki-67 staining among LMP and G1 tumors (Terlikowski et al, 1999), consistent with our observation that LMPs and a majority of G1 carcinomas do not express detectable levels of Ki-67, either by array profiling of by immunostaining with Ki-67 antibodies.…”

Section: Discussionmentioning

confidence: 99%

Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential

et al. 2004

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Profiles of gene transcription have begun to delineate the molecular basis of ovarian cancer, including distinctions between carcinomas of differing histology, tumor progression and patient outcome. However, the similarities and differences among the most commonly diagnosed noninvasive borderline (low malignant potential, LMP) lesions and invasive serous carcinomas of varying grade (G1, G2 and G3) have not yet been explored. Here, we used oligonucleotide arrays to profile the expression of 12 500 genes in a series of 57 predominantly stage III serous ovarian adenocarcinomas from 52 patients, eight with borderline tumors and 44 with adenocarcinomas of varying grade. Unsupervised and supervised analyses showed that LMP lesions were distinct from high-grade serous adenocarcinomas, as might be expected; however, well-differentiated (G1) invasive adenocarcinomas showed a strikingly similar profile to LMP tumors as compared to cancers with moderate (G2) or poor (G3) cellular differentiation, which were also highly similar. Comparative genomic hybridization of an independent cohort of five LMP and 63 invasive carcinomas of varying grade demonstrated LMP and G1 were again similar, exhibiting significantly less chromosomal aberration than G2/G3 carcinomas. A majority of LMP and G1 tumors were characterized by high levels of p21/WAF1, with concomitant expression of cell growth suppressors, gadd34 and BTG-2. In contrast, G2/G3 cancers were characterized by the expression of genes associated with the cell cycle and by STAT-1-, STAT-3/JAK-1/2-induced gene expression. The distinction between the LMP-G1 and G2-G3 groups of tumors was highly correlated to patient outcome (v 2 for equivalence of death rates ¼ 7.681189; P ¼ 0.0056, log-rank test). Our results are consistent with the recent demonstration of a poor differentiation molecular 'meta-signature' in human cancer, and underscore a number of cell-cycle-and STAT-associated targets that may prove useful as points of therapeutic intervention for those patients with aggressive disease.

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“…19,20,[23][24][25]28,29,39,42,46,[49][50][51]53,58,[61][62][63][64]66,[71][72][73][74][76][77][78][79]82,83,85,87,90,95,97,99,103,104,106,109,110,114 Overall, p53 was detected in 39% of the Stage I/II tumors and 55% of the Stage III/IV tumors ( Again, although antibody specific estimates by tumor grade varied considerably (data not shown), a consistent pattern emerged. Overall, the proportion of tumors positive for p53 was lowest among the Grade 1 tumors and highest among the Grade 3 tumors (Fig.…”

Section: Carcinomamentioning

confidence: 99%

A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors

Kmet

Cook

Magliocco

2003

Cancer

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Das rationale Design niedermolekularer Verbindungen, die selektiv auf eine definierte RNA wirken, ist eine schwierige Aufgabe; solche Sonden könnten aber die zeitlich hochaufgelöste Untersuchung von RNA‐Funktionen in Zellen ermöglichen. In der Zuschrift auf identifizieren R. Rodriguez, S. Balasubramanian et al. mit In‐situ‐Klickchemie eine niedermolekulare Substanz, die selektiv mit Telomerwiederholungseinheiten enthaltender RNA (TERRA) über die Erkennung der G‐Quadruplex‐Struktur wechselwirkt. Mit demselben Ansatz wurde ein verwandtes Analogon erkannt, das hoch effizient die entsprechende DNA adressiert.

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p53 Expression in Epithelial Ovarian Neoplasms: Relationship to Clinical and Pathological Parameters, Ki-67 Expression and Flow Cytometry

Cited by 87 publications

References 0 publications

p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer

p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer

Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential

A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors

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