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BMC Cancer. 2018 Jun 25;18(1):684. doi: 10.1186/s12885-018-4591-3.

High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma.

Author information

1
Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway. katharina.bischof@uib.no.
2
Department of Gynecology and Obstetrics, Haukeland University Hospital, N-5021, Bergen, Norway. katharina.bischof@uib.no.
3
Department of Oncology, Haukeland University Hospital, 5021, Bergen, Norway.
4
Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.
5
Department of Pathology, Haukeland University Hospital, 5021, Bergen, Norway.
6
CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.
7
Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway.
8
Department of Gynecology and Obstetrics, Haukeland University Hospital, N-5021, Bergen, Norway.
9
Bergen Gynaecologic Cancer Research Group, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
10
Department of Internal Medicine, Haematology Section, Haukeland University Hospital, 5021, Bergen, Norway.

Abstract

BACKGROUND:

Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial carcinoma. Large-scale comprehensive efforts have resulted in an improved molecular understanding of its pathogenesis, and the p53 pathway has been proposed as a key player and is potentially targetable. Here we attempt to further portray the p53 pathway in USC by assessing p53 isoform expression.

METHODS:

We applied quantitative Real-Time PCRs (RT-qPCR) for expression analyses of total p53 mRNA as well as quantitative distinction of p53β, p53γ, and the total mRNA of amino-terminal truncated Δ40p53 and Δ133p53 in a retrospective cohort of 37 patients with USC. TP53 mutation status was assessed by targeted massive parallel sequencing. Findings were correlated with clinical data.

RESULTS:

The p53 isoform expression landscape in USCs was heterogeneous and dominated by total Δ133p53, while the distinct p53β and p53γ variants were found at much lower levels. The isoform expression profiles varied between samples, while their expression was independent of TP53 mutation status. We found high relative p53γ expression to be associated with reduced progression-free survival (PFS).

CONCLUSIONS:

This is the first indication that elevated p53γ expression is associated with reduced PFS in USC. This single-center study may offer some insight in the landscape of p53 isoform expression in USC, but further validation studies are crucial to understand the context-dependent and tissue-specific role of the p53 isoform network in gynecological cancer.

KEYWORDS:

Biomarker; RT-qPCR; Type II endometrial cancer; Uterine serous carcinoma; mRNA expression analysis; p53 isoforms

PMID:
29940909
PMCID:
PMC6019524
DOI:
10.1186/s12885-018-4591-3
[Indexed for MEDLINE]
Free PMC Article

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