CIP2A is a marker of reduced survival in serous ovarian cancer patients
Camilla Böckelman
Finland 
7 slide(s) – 00:04:16 – English – 2009-10-11
CIP2A is a marker of reduced survival in serous ovarian cancer patients
Camilla Böckelman [1,2,3], Heini Lassus [4], Annabrita Hemmes [1,2], Jukka Westermarck [5,6], Arto Leminen [4], Caj Haglund [3], Ralf Bützow [2,4], Ari Ristimäki [1,2,7]
[1] Genome-Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
[2] Department of Pathology, HUSLAB and Haartman Institute, University of Helsinki, Helsinki, Finland.
[3] Department of Surgery, University of Helsinki, Helsinki, Finland.
[4] Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland.
[5] Institute of Medical Technology, University of Tampere and Tampere University.
[6] Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
[7] Department of Pathology, Institute of Diagnostics, University of Oulu and Oulu University Hospital, Oulu, Finland.
Abstract
Cancerous inhibitor of PP2A (CIP2A) is a recently identified human oncoprotein that stabilizes c-Myc protein by inhibiting protein phosphatase 2A (PP2A) mediated dephosphorylation of c-Myc.
Tissue microarrays consisting of 524 consecutive patients treated for serous ovarian carcinoma at the Department of Obstetrics and Gynecology of the Helsinki University Central Hospital were analyzed for presence of CIP2A by immunohistochemistry. The association of CIP2A expression with survival was evaluated according to the Kaplan-Meier method.
Our results demonstrate for the first time that CIP2A immunopositivity is a marker of reduced disease-specific survival in ovarian cancer patients (P<0.0001). Positive CIP2A expression was significantly more frequent in specimens with high grade (P<0.0001), and in patients who had ascites (P=0.0043). In addition, there was an association between CIP2A expression and aberrant p53 (P<0.0001), high proliferation index (Ki-67; P<0.0001), and aneuploidity (P=0.001).
The poor prognosis of CIP2A immunopositive patients is largely affected by the association to high-grade tumors, which has been shown to be an independent prognostic factor. Moreover, the association of CIP2A immunopositivity with markers that have previously been shown to correlate with advanced disease (aberrant p53 expression, high proliferation index and aneuploidity) suggests that CIP2A immunopositivity might be a marker of aggressive tumor behavior.
In conclusion, our results demonstrate that immunopositive CIP2A is a novel marker of reduced survival in patients with serous ovarian carcinoma. Furthermore, the associations between CIP2A expression and markers of aggressive disease suggests that CIP2A might be an oncoprotein in the so-called type II high-grade pathway of serous ovarian carcinomas.
1. Junttila MR et al: CIP2A inhibits PP2A in human malignancies. Cell 2007.
2. Junttila MR, Westermarch J: Mechanisms of MYC stabilization in human malignances. Cell Cycle 2007.
3. Khanna A, Böckelman C et al: MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst 2009.
4. Come C et al: CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res 2009.
5. Soo Hoo L et al: Cloning and characterization of a novel 90 kDa “companion” auto-antigen of p62 overexpressed in cancer. Oncogene 2002.
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