Sage Journals: Discover world-class research

Abstract

Objective

To evaluate the apurinic/apyrimidinic endonuclease 1 (APE1) expression in sinonasal squamous cell carcinomas (SCC) and to examine the correlation between APE1 expression patterns and various clinicopathological factors associated with sinonasal SCC that include SCC with inverted papilloma (SCCwIP) and SCC alone.

Study Design

Case-control study.

Setting

Chungnam National University Hospital.

Subjects and Methods

The expressions of APE1 were analyzed by means of immunohistochemistry in 30 sinonasal SCC, including 14 SCC patients associated with IP and 16 patients with SCC alone. A total of 19 patients who had been diagnosed with chronic rhinosinusitis with nasal polyposis and who required endoscopic sinus surgery were used as the control group. The degrees of APE1 expression were analyzed with respect to the following clinicopathologic variables: age, sex, T stage, histologic differentiation, distant metastasis, and recurrence.

Results

Cytoplasmic staining of APE1 was significantly higher in SCC compared with SCCwIP (68.75% vs 14.29%). Cytoplasmic staining of APE1 was significantly associated with T stage (P = .044) in SCC and histologic grade (P = .0025) in sinonasal SCC. Nuclear staining of APE1 was significantly associated with distant metastasis (P = .022) in SCC.

Conclusion

These results suggest that the nuclear and cytoplasmic expression of APE1 may be related to tumor invasiveness and prognosis in sinonasal SCC. The suppression of APE1 expression can potentially be a new target for future sinonasal SCC therapies.

Keywords

squamous cell carcinoma inverted papilloma APE-1 tumor invasion metastasis

Get full access to this article

View all access options for this article.

References

Batsakis

Rice

Solomon

. The pathology of head and neck tumors: squamous and mucous-gland carcinomas of nasal cavity, paranasal sinuses, and larynx, part 6. Head Neck Surg. 1980;2:497-508.

Dulguerov

Jacobsen

Allal

Lehmann

Calcaterra

. Nasal and paranasal sinus carcinoma: are we making progress? Cancer. 2001;92:3012-3029.

Demple

Harrison

. Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem. 1994;63:915-948.

Kishor

Anil

Sankar

. Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein. Antioxid Redox Signal. 2009;11:621-638.

Gossage

Fareed

. Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers. Cancer Res. 2010;102:704-709.

Grigory

. Base excision repair targets for cancer therapy. Cancer Res. 2011;1:845-851.

Carlos

Iwakuma

Izumi

. Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway. Oncogene. 2009;23:1616-1625.

Melissa

Yanlin

Rajeshkumar

. Impact of APE1/Ref-1 redox inhibition on pancreatic tumor growth. Mol Cancer Ther. 2011;10:1698-1708.

Lavertu

Roberts

Kraus

. Squamous cell carcinoma of the paranasal sinuses: the Cleveland clinic experience 1977-1986. Laryngocsope. 1989;99:1130-1136.

10.

Tanvetyanon

Qin

Padhya

Kapoor

McCaffrey

Trotti

. Survival outcomes of squamous cell carcinoma arising from sinonasal inverted papilloma: reported 6 cases with systemic review and analysis. Am J Otolaryngol. 2009;30:38-43.

11.

Lesperance

Esclamado

. Squamous cell carcinoma arising in inverted papilloma. Laryngoscope. 1995;105:178-183.

12.

Vrabec

. The inverted Schneiderian papilloma: a 25-year study. Laryngoscope. 1994;104:582-605.

13.

Mendenhall

Hinerman

Malyapa

. Inverted papilloma of the nasal cavity and paranasal sinuses. Am J Clin Oncol. 2007;30:560-563.

14.

Mannetje

Kogevinas

Luce

. Sinonasal cancer, occupation, and tobacco smoking in European women and men. Am J Ind Med. 1999;36:101-107.

15.

Khademi

Moradi

Hoseini

Mohammadianpanah

. Malignant neoplasms of the sinonasal tract: report of 71 patients and literature review and analysis. Oral Maxillofac Surg. 2009;13:191-199.

16.

Meira

Cheo

Hammer

Burns

Reis

Friedberq

. Genetic interaction between HAP1/REF-1 and p53. Nat Genet. 1997;17:145.

17.

Zaky

Busso

Izumi

. Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage. Nucleic Acids Res. 2008;36:1555-1566.

18.

Bao

McLendon

. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756-760.

19.

Robertson

Bullock

. Altered expression of Ape1/ref-1 in germ cell tumors and overexpression in NT2 cells confers resistance to bleomycin and radiation. Cancer Res. 2001;61:2220-2225.

20.

Yang

Irani

Heffron

Jurnak

Meyskens

Jr . Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) in human melanoma and identification of the therapeutic potential of resveratrol as an APE/Ref-1 inhibitor. Mol Cancer Ther. 2005;4:1923-1935.

21.

Wang

Xiang

Yang

. APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells. Lung Cancer. 2009;66:298-304.

22.

Koukourakis

Giatromanolaki

Kakolyris

. Nuclear expression of human apurinic/apyrimidinic endonuclease (HAP1/Ref-1) in head-and-neck cancer is associated with resistance to chemoradiotherapy and poor outcome. Int J Radiat Oncol Biol Phys. 2001;50:27-36.

23.