Δ133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer
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Δ133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer. / Hofstetter, G; Berger, A; Schuster, E; Wolf, A; Hager, G; Vergote, I; Cadron, I; Sehouli, J; Braicu, E I; Mahner, S; Speiser, P; Marth, C; Zeimet, A G; Ulmer, H; Zeillinger, R; Concin, N.
In: BRIT J CANCER, Vol. 105, No. 10, 08.11.2011, p. 1593-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Δ133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer
AU - Hofstetter, G
AU - Berger, A
AU - Schuster, E
AU - Wolf, A
AU - Hager, G
AU - Vergote, I
AU - Cadron, I
AU - Sehouli, J
AU - Braicu, E I
AU - Mahner, S
AU - Speiser, P
AU - Marth, C
AU - Zeimet, A G
AU - Ulmer, H
AU - Zeillinger, R
AU - Concin, N
N1 - 2011 Cancer Research UK
PY - 2011/11/8
Y1 - 2011/11/8
N2 - BACKGROUND: We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53.METHODS: This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT-qPCR.RESULTS: Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P=0.016, 95% CI: 0.362-0.899) and overall survival (hazard ratio=0.365, P=0.004, 95% CI: 0.182-0.731) in patients with p53 mutant ovarian cancer (n=121). High Δ40p53 expression was associated with favourable tumour grading (P=0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P=0.029), but not overall survival (43.1 vs 33.6 months, P=0.139), in patients with p53 wild-type cancer (n=33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases.CONCLUSION: Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network.
AB - BACKGROUND: We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53.METHODS: This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT-qPCR.RESULTS: Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P=0.016, 95% CI: 0.362-0.899) and overall survival (hazard ratio=0.365, P=0.004, 95% CI: 0.182-0.731) in patients with p53 mutant ovarian cancer (n=121). High Δ40p53 expression was associated with favourable tumour grading (P=0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P=0.029), but not overall survival (43.1 vs 33.6 months, P=0.139), in patients with p53 wild-type cancer (n=33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases.CONCLUSION: Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Female
KW - Genes, p53
KW - Humans
KW - Middle Aged
KW - Mutation
KW - Ovarian Neoplasms
KW - Prognosis
KW - Prospective Studies
KW - Real-Time Polymerase Chain Reaction
KW - Tumor Markers, Biological
KW - Tumor Suppressor Protein p53
U2 - 10.1038/bjc.2011.433
DO - 10.1038/bjc.2011.433
M3 - SCORING: Journal article
C2 - 22009029
VL - 105
SP - 1593
EP - 1599
JO - BRIT J CANCER
JF - BRIT J CANCER
SN - 0007-0920
IS - 10
ER -