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Cytoplasmic iASPP Expression as a Novel Prognostic Indicator in Oral Cavity Squamous Cell Carcinoma

  • Head and Neck Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a key inhibitor of tumor suppressor p53 that is overexpressed in several human cancers; however, its role in oral cavity squamous cell carcinomas (OSCC) remains unknown. The present study investigated the prognostic role of iASPP in patients with OSCC.

Methods

This study included 186 OSCC patients who underwent curative surgery at our institution between 2000 and 2011. Cytoplasmic and nuclear iASPP expression were examined separately by immunohistochemistry, and dichotomized to low and high. Clinicopathological variables associated with locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were identified by univariate and multivariate analyses.

Results

Patients were followed-up for a median period of 74 months (range 16–166 months), and 5-year LRC, DFS, and OS was 73.6, 70.2, and 75.3 %, respectively. High iASPP immunostaining reactivity was detected in the cytoplasm and nucleus in 132 (71.0 %) and 93 (50.0 %) patients, respectively. In univariate analysis, pathologic nodal metastasis, advanced overall stage III–IV, lymphovascular invasion, and cytoplasmic iASPP were significantly associated with poor LRC, DFS, and OS (p < 0.05). High-grade and positive resection margins were significant factors associated with poor DFS and OS (p < 0.02). In multivariate analysis, N classification, lymphovascular invasion, and cytoplasmic iASPP expression remained independent variables for LRC, DFS, and OS (p < 0.05).

Conclusion

High iASPP expression in the tumor cell cytoplasm is associated with poor outcomes of OSCC patients in terms of recurrence and survival, suggesting a role for iASPP as a novel biomarker and therapeutic target for OSCC.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  2. Tankere F, Camproux A, Barry B, Guedon C, Depondt J, Gehanno P. Prognostic value of lymph node involvement in oral cancers: a study of 137 cases. Laryngoscope. 2000;110:2061–5.

    Article  CAS  PubMed  Google Scholar 

  3. Sano D, Myers JN. Metastasis of squamous cell carcinoma of the oral tongue. Cancer Metastasis Rev. 2007;26:645–62.

    Article  CAS  PubMed  Google Scholar 

  4. Murthy V, Agarwal JP, Laskar SG, et al. Analysis of prognostic factors in 1180 patients with oral cavity primary cancer treated with definitive or adjuvant radiotherapy. J Cancer Res Ther 2010;6:282–9.

    Article  CAS  PubMed  Google Scholar 

  5. Funk GF, Karnell LH, Robinson RA, Zhen WK, Trask DK, Hoffman HT. Presentation, treatment, and outcome of oral cavity cancer: a national cancer data base report. Head Neck. 2002;24:165–80.

    Article  PubMed  Google Scholar 

  6. Bergamaschi D, Samuels Y, O’Neil NJ, et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat Genet. 2003;33:162–7.

    Article  CAS  PubMed  Google Scholar 

  7. Trigiante G, Lu X. ASPP and cancer. Nat Rev Cancer. 2006;6:217–26.

    Article  CAS  PubMed  Google Scholar 

  8. Cai Y, Qui S, Gao X, Gu SZ, Liu ZJ. iASPP inhibits p53-independent apoptosis by inhibiting transcriptional activity of p63/p73 on promoters of proapoptotic genes. Apoptosis. 2012;17:777–83.

    Article  CAS  PubMed  Google Scholar 

  9. Samuels-Lev Y, O’Connor DJ, Bergamaschi D, et al. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell. 2001;8:781–94.

    Article  CAS  PubMed  Google Scholar 

  10. Alsafadi S, Tourpin S, André F, Vassal G, Ahomadegbe JC. p53 family: at the crossroads in cancer therapy. Curr Med Chem. 2009; 16:4328–44.

    Article  CAS  PubMed  Google Scholar 

  11. Bell HS, Ryan KM. iASPP inhibition: increased options in targeting the p53 family for cancer therapy. Cancer Res. 2008;68:4959–62.

    Article  CAS  PubMed  Google Scholar 

  12. Lu M, Breyssens H, Salter V, et al. Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP. Cancer Cell. 201;23:618–33.

  13. Zhang X, Wang M, Zhou C, Chen S, Wang J. The expression of iASPP in acute leukemias. Leuk Res. 2005;29:179–83.

    Article  CAS  PubMed  Google Scholar 

  14. Chen J, Xie F, Zhang L, Jiang WG. iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway. BMC Cancer. 2010;10:694.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Lu B, Guo H, Zhao J, et al. Increased expression of iASPP, regulated by hepatitis B virus X protein-mediated NF-kappaB activation, in hepatocellular carcinoma. Gastroenterology. 2010;139:2183–94.

    Article  CAS  PubMed  Google Scholar 

  16. Jiang L, Siu MK, Wong OG, et al. iASPP and chemoresistance in ovarian cancers: effects on paclitaxel mediated mitotic catastrophe. Clin Cancer Res. 2011;17:6924–33.

    Article  CAS  PubMed  Google Scholar 

  17. Liu WK, Jiang XY, Ren JK, Zhang ZX. Expression pattern of the ASPP family members in endometrial endometrioid adenocarcinoma. Onkologie. 2010;33(10):500–3.

    Article  PubMed  Google Scholar 

  18. Cao L, Huang Q, He J, Lu J, Xiong Y. Elevated expression of iASPP correlates with poor prognosis and chemoresistance/radioresistance in FIGO Ib1-IIa squamous cell cervical cancer. Cell Tissue Res. 2013;352:361–9.

    Article  CAS  PubMed  Google Scholar 

  19. Liu Z, Zhang X, Huang D, et al. Elevated expression of iASPP in head and neck squamous cell carcinoma and its clinical significance. Med Oncol. 2012;29:3381–8.

    Article  CAS  PubMed  Google Scholar 

  20. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual. 7th ed. New York: Springer-Verlag; 2010:29–40.

    Google Scholar 

  21. Zhang B, Xiao HJ, Chen J, Tao X, Cai LH. Inhibitory member of the apoptosis-stimulating protein of p53 (ASPP) family promotes growth and tumorigenesis in human p53-deficient prostate cancer cells. Prostate Cancer Prostatic Dis. 2011;14:219–24.

    Article  CAS  PubMed  Google Scholar 

  22. Chikh A, Matin RN, Senatore V, et al. iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia. EMBO J. 2011;30:4261–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Zhao WH, Wu SQ, Zhang YD. Downregulation of miR-124 promotes the growth and invasiveness of glioblastoma cells involving upregulation of PPP1R13L. Int J Mol Med. 2013;32:101–7.

    PubMed  Google Scholar 

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Acknowledgment

This study was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea, which is funded by the Ministry of Education, Science and Technology (Grant No. NRF-2012R1A1A2002039), Seoul, Korea (Jong-Lyel Roh).

Disclosure

Ji Won Kim, Jong-Lyel Roh, Yangsoon Park, Kyung-Ja Cho, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim have declared no conflicts of interest.

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Correspondence to Jong-Lyel Roh MD.

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Kim, J.W., Roh, JL., Park, Y. et al. Cytoplasmic iASPP Expression as a Novel Prognostic Indicator in Oral Cavity Squamous Cell Carcinoma. Ann Surg Oncol 22, 662–669 (2015). https://doi.org/10.1245/s10434-014-4003-0

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  • DOI: https://doi.org/10.1245/s10434-014-4003-0

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