High CIP2A Immunoreactivity is an Independent Prognostic Indicator in Early-stage Tongue Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2011 May 26

PMID 21610708

Citations 29

Authors

C Bockelman

J Hagstrom

L K Makinen

H Keski-Santti

V Hayry

J Lundin

T Atula

A Ristimaki

C Haglund

Affiliations

Soon will be listed here.

Abstract

Background: No reliable prognostic markers exist for squamous cell carcinoma of the tongue, and its prognosis can even in early stages be unpredictable and survival poor despite treatment. A potential marker is oncoprotein cancerous inhibitor of PP2A (CIP2A), which acts as a prognostic marker in gastric and non-small cell lung cancers.

Methods: We collected specimens of 73 stage T1N0M0 and T2N0M0 oral squamous cell carcinomas of the tongue, as well as samples from normal oral mucosa, dysplastic lesions, and invasive carcinomas (n=39). All samples were stained for CIP2A by immunohistochemistry. Survival curves were constructed according to the Kaplan-Meier method. The Cox proportional hazard model served for univariate and multivariate survival analysis.

Results: High CIP2A immunoreactivity predicted poor survival in tongue cancer patients (P=0.027, logrank test). In multivariate survival analysis, CIP2A was an independent prognostic factor (HR 2.02, 95% confidence interval 1.07-3.82, P=0.030). Cytoplasmic CIP2A expression was higher in severe dysplasia than in mild dysplasia.

Conclusion: Our results suggest that high CIP2A expression characterises aggressive disease. Acting as a prognostic marker it might be of help when choosing patients for adjuvant treatment in tongue cancer patients.

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References

Come C, Laine A, Chanrion M, Edgren H, Mattila E, Liu X . CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 2009; 15(16):5092-100. DOI: 10.1158/1078-0432.CCR-08-3283. View

Katz J, Jakymiw A, Ducksworth M, Stewart C, Bhattacharyya I, Cha S . CIP2A expression and localization in oral carcinoma and dysplasia. Cancer Biol Ther. 2010; 10(7):694-9. PMC: 3230513. DOI: 10.4161/cbt.10.7.12895. View

Massarelli E, Liu D, Lee J, El-Naggar A, Lo Muzio L, Staibano S . Akt activation correlates with adverse outcome in tongue cancer. Cancer. 2005; 104(11):2430-6. DOI: 10.1002/cncr.21476. View

Keski-Santti H, Atula T, Tornwall J, Koivunen P, Makitie A . Elective neck treatment versus observation in patients with T1/T2 N0 squamous cell carcinoma of oral tongue. Oral Oncol. 2005; 42(1):96-101. DOI: 10.1016/j.oraloncology.2005.06.018. View

Junttila M, Puustinen P, Niemela M, Ahola R, Arnold H, Bottzauw T . CIP2A inhibits PP2A in human malignancies. Cell. 2007; 130(1):51-62. DOI: 10.1016/j.cell.2007.04.044. View

Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Kochli O . Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol. 2001; 159(6):2249-56. PMC: 1850582. DOI: 10.1016/S0002-9440(10)63075-1. View

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S . Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998; 4(7):844-7. DOI: 10.1038/nm0798-844. View

Kallioniemi O, Wagner U, Kononen J, Sauter G . Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet. 2001; 10(7):657-62. DOI: 10.1093/hmg/10.7.657. View

Soo Hoo L, Zhang J, Chan E . Cloning and characterization of a novel 90 kDa 'companion' auto-antigen of p62 overexpressed in cancer. Oncogene. 2002; 21(32):5006-15. DOI: 10.1038/sj.onc.1205625. View

10.

Guenebeaud C, Goldschneider D, Castets M, Guix C, Chazot G, Delloye-Bourgeois C . The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Mol Cell. 2010; 40(6):863-76. DOI: 10.1016/j.molcel.2010.11.021. View

11.

Chen K, Liu C, Lin Y, Yu H, Liu T, Hou D . CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells. Oncogene. 2010; 29(47):6257-66. DOI: 10.1038/onc.2010.357. View

12.

Sanchez-Cespedes M, Esteller M, Wu L, Yoo G, Koch W, Jen J . Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res. 2000; 60(4):892-5. View

13.

Hayry V, Makinen L, Atula T, Sariola H, Makitie A, Leivo I . Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue. Br J Cancer. 2010; 102(5):892-7. PMC: 2833245. DOI: 10.1038/sj.bjc.6605544. View

14.

Dong Q, Wang Y, Dong X, Li Z, Tang Z, Cui Q . CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol. 2010; 18(3):857-65. DOI: 10.1245/s10434-010-1313-8. View

15.

Gozuacik D, Kimchi A . DAPk protein family and cancer. Autophagy. 2006; 2(2):74-9. DOI: 10.4161/auto.2.2.2459. View

16.

Qu W, Li W, Wei L, Xing L, Wang X, Yu J . CIP2A is overexpressed in esophageal squamous cell carcinoma. Med Oncol. 2010; 29(1):113-8. DOI: 10.1007/s12032-010-9768-9. View

17.

Bello I, Soini Y, Salo T . Prognostic evaluation of oral tongue cancer: means, markers and perspectives (I). Oral Oncol. 2010; 46(9):630-5. DOI: 10.1016/j.oraloncology.2010.06.006. View

18.

Khanna A, Bockelman C, Hemmes A, Junttila M, Wiksten J, Lundin M . MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 2009; 101(11):793-805. DOI: 10.1093/jnci/djp103. View

19.

Bello I, Soini Y, Salo T . Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II). Oral Oncol. 2010; 46(9):636-43. DOI: 10.1016/j.oraloncology.2010.06.008. View

20.

Keski-Santti H, Atula T, Tikka J, Hollmen J, Makitie A, Leivo I . Predictive value of histopathologic parameters in early squamous cell carcinoma of oral tongue. Oral Oncol. 2007; 43(10):1007-13. DOI: 10.1016/j.oraloncology.2006.11.015. View