Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy

Hayashi,Jyunichi; Sakata,Koh-Ichi; Someya,Masanori; Matsumoto,Yoshihisa; Satoh,Masaaki; Nakata,Kensei; Hori,Masakazu; Takagi,Masaru; Kondoh,Atsushi; Himi,Tetsuo; Hareyama,Masato

doi:10.3892/ol.2012.674

Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy

Authors:
- Jyunichi Hayashi
- Koh-Ichi Sakata
- Masanori Someya
- Yoshihisa Matsumoto
- Masaaki Satoh
- Kensei Nakata
- Masakazu Hori
- Masaru Takagi
- Atsushi Kondoh
- Tetsuo Himi
- Masato Hareyama
View Affiliations

Affiliations: Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan, Tokyo Institute of Technology, Research Laboratory for Nuclear Reactors, Tokyo, Japan, Division of Clinical Pathology, NTT Sapporo Hospital, Sapporo, Japan, Department of Otolaryngology, Sapporo Medical University, School of Medicine, Hokkaido, Japan
Published online on: April 5, 2012 https://doi.org/10.3892/ol.2012.674
Pages: 151-155

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation. Non-homologous end-joining (NHEJ) is a key mechanism of DNA DSB repair. The immunohistochemical analysis of proteins involved in NHEJ may have potential as a predictive assay for tumor radiosensitivity. We examined the correlation between the expression of proteins involved in DNA DSB in biopsy specimens and the results of chemoradiotherapy in hypopharyngeal cancers. Fifty-seven patients with previously untreated squamous cell carcinoma of the hypopharynx were treated between March 2002 and December 2009. Most patients (75%) had stage III or IV disease. The chemotherapy consisted of cisplatin plus 5FU or S-1. A tumor dose of 50 Gy was usually administered to the primary tumor and regional lymph nodes. Doses of 10-20 Gy were usually added to the primary tumor with reduced fields after 50 Gy. The 5-year disease-free survival rate was 100% for patients in stage I, 90% in stage II, 64% in stage III and 50% in stage IV. In stages I-III, patients with a lower expression of Ku70 or XRCC4 tended to have better locoregional control. These results indicated that a lower expression of Ku70 or XRCC4 may be correlated with higher radiosensitivity. Two patients had distant metastasis alone, of which one had 0% expression of Ku70 and the other had 0% expression of Ku86. The absence of Ku70 or Ku86 expression indicates low DNA-PK activity. Low DNA-PK activity due to a low expression of Ku may result in the genetic alteration of cancer cells, leading to a higher tendency of distant metastasis. This finding suggests that proteins involved in NHEJ may have an impact on the treatment results of chemoradiotherapy in hypopharyngeal cancer.

View Figures

View References

1	Adelstein DJ, Li Y, Adams GL, et al: An intergroup study phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 21:92–98. 2003. View Article : Google Scholar
2	Denis F, Garaud P, Bardet E, et al: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 22:69–76. 2004. View Article : Google Scholar
3	Forastiere AA, Goepfert H, Maor M, et al: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 349:2091–2098. 2003. View Article : Google Scholar : PubMed/NCBI
4	Hall EJ: DNA strand breaks and chromosomal aberrations. Radiobiology for the Radiologist. Hall EJ and Giaccia AM: 6th edition. Lippincott Williams & Wilkins; Philadelphia: pp. 16–29. 2006
5	Polo SE and Jackson SP: Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modification. Gene Dev. 25:409–433. 2011. View Article : Google Scholar : PubMed/NCBI
6	Lees-Miller SP: The DNA-dependent protein kinase, DNA-PK: 10 years and no ends in sight. Biochem Cell Biol. 74:503–512. 1996.PubMed/NCBI
7	Jeggo PA: Identification of genes involved in repair of DNA double-strand breaks in mammalian cells. Radiat Res. 150:S80–S91. 1998. View Article : Google Scholar : PubMed/NCBI
8	Komuro Y, Watanabe T, Hosoi Y, et al: The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer. 95:1199–1205. 2002. View Article : Google Scholar : PubMed/NCBI
9	Zhao HJ, Hosoi Y, Miyachi H, et al: DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines. Clin Cancer Res. 6:1073–1078. 2000.PubMed/NCBI
10	Sakata K, Matsumoto Y, Tauchi H, et al: Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues. Int J Radiat Oncol Biol Phys. 49:161–167. 2001. View Article : Google Scholar : PubMed/NCBI
11	Kamdar RP and Matsumoto Y: Radiation-induced XRCC4 association with chromatin DNA analyzed by biochemical fractionation. J Radiat Res. 51:303–313. 2010. View Article : Google Scholar : PubMed/NCBI
12	Sakata K, Someya M, Nagakura H, et al: Brachytherapy for oral tongue cancer: an analysis of treatment results with various biological markers. Jpn J Clin Oncol. 38:402–407. 2008. View Article : Google Scholar : PubMed/NCBI
13	Pointreau Y, Garaud P, Chapet S, et al: Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 101:498–506. 2009. View Article : Google Scholar
14	Posner MR, Hershock DM, Blajman CR, et al: Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. New Engl J Med. 25:1705–1715. 2007. View Article : Google Scholar : PubMed/NCBI
15	Someya M, Sakata K, Matsumoto Y, Satoh M, Narimatsu H and Hareyama M: Immunohistochemical analysis of Ku70/86 expression of breast cancer tissues. Oncol Rep. 18:1483–1487. 2007.PubMed/NCBI
16	Hosoi Y, Watanabe T, Nakagawa K, et al: Up-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancer. Int J Oncol. 25:461–468. 2004.PubMed/NCBI
17	Raybaud-Diogene H, Fortin A, Morency R, Roy J, Monteil RA and Tetu B: Markers of radioresistance in squamous cell carcinomas of the head and neck: a clinicopathologic and immunohistochemical study. J Clin Oncol. 15:1030–1038. 1997.PubMed/NCBI
18	Okuno Y, Nishimura Y, Kashu I, Ono K and Hiraoka M: Prognostic values of proliferating cell nuclear antigen (PCNA) and Ki-67 for radiotherapy of oesophageal squamous cell carcinomas. Br J Cancer. 80:387–395. 1999. View Article : Google Scholar : PubMed/NCBI
19	Nakano T and Oka K: Differential values of Ki-67 index and mitotic index of proliferating cell population. An assessment of cell cycle and prognosis in radiation therapy for cervical cancer. Cancer. 72:2401–2408. 1993. View Article : Google Scholar : PubMed/NCBI
20	Burma S, Chen BPC and Chen DJ: Role of non-homologous end joining (NHEJ) in maintaining genomic integrity. DNA Repair. 5:1042–1048. 2006. View Article : Google Scholar : PubMed/NCBI
21	Someya M, Sakata K, Matsumoto Y, et al: The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer. Carcinogenesis. 27:117–122. 2006. View Article : Google Scholar : PubMed/NCBI