Copy number increase of oncoprotein CIP2A is associated with poor patient survival in human head and neck squamous cell carcinoma

Johannes Routila; Türker Bilgen; Outi Saramäki; Reidar Grénman; Tapio Visakorpi; Jukka Westermarck; Sami Ventelä

doi:10.1111/jop.12372

Copy number increase of oncoprotein CIP2A is associated with poor patient survival in human head and neck squamous cell carcinoma

J Oral Pathol Med. 2016 May;45(5):329-37. doi: 10.1111/jop.12372. Epub 2015 Oct 5.

Authors

Johannes Routila¹, Türker Bilgen^{2

3}, Outi Saramäki^{2

4}, Reidar Grénman⁵, Tapio Visakorpi^{2

4}, Jukka Westermarck^{1

6}, Sami Ventelä^{1

5}

Affiliations

¹ Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
² Prostate Cancer Research Center, Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland.
³ Research and Application Centre for Scientific and Technological Investigations (NABILTEM), Namik Kemal University, Tekirdag, Turkey.
⁴ Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
⁵ Department of Otorhinolaryngology - Head and Neck Surgery, Turku University Hospital, Turku, Finland.
⁶ Department of Pathology, University of Turku, Turku, Finland.

PMID: 26436875
DOI: 10.1111/jop.12372

Abstract

Background: CIP2A, an inhibitor of PP2A tumour suppressor function, is a widely overexpressed biomarker of aggressive disease and poor therapy response in multiple human cancer types.

Methods: CIP2A and DPPA4 copy number alterations and expression were analysed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in different cell lines and a tissue microarray of 52 HNSCC patients. Results were correlated with patient survival and other clinicopathological data.

Results: CIP2A and DPPA4 copy number increase occurred at a relatively high frequency in human HNSCC patient samples. CIP2A but not DPPA4 FISH status was significantly associated with patient survival. CIP2A detection by combining IHC with FISH yielded superior resolution in the prognostication of HNSCC.

Conclusions: CIP2A copy number increase is associated with poor patient survival in human HNSCC. We suggest that the reliability and prognostic value of CIP2A detection can be improved by performing FISH analysis to CIP2A IHC positive tumours.

Keywords: CIP2A; DPPA4; head and neck; in situ hybridisation; protein phosphatase 2a; squamous cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoantigens / biosynthesis*
Autoantigens / genetics*
Biomarkers, Tumor / biosynthesis
Biomarkers, Tumor / genetics
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Disease-Free Survival
Female
Gene Dosage
HeLa Cells
Head and Neck Neoplasms / genetics*
Head and Neck Neoplasms / metabolism
Head and Neck Neoplasms / pathology
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence / methods
Intracellular Signaling Peptides and Proteins
Male
Membrane Proteins / biosynthesis*
Membrane Proteins / genetics*
Middle Aged
Nuclear Proteins / biosynthesis
Nuclear Proteins / genetics
Prognosis
Reproducibility of Results
Squamous Cell Carcinoma of Head and Neck
Tissue Array Analysis / methods

Substances

Autoantigens
Biomarkers, Tumor
CIP2A protein, human
DPPA4 protein, human
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Nuclear Proteins