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. 2010 Jun 8;102(12):1778-85.
doi: 10.1038/sj.bjc.6605707. Epub 2010 May 25.

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

W J Pattje  1 , E Schuuring, M F Mastik, L Slagter-Menkema, M L Schrijvers, S Alessi, B F A M van der Laan, J L N Roodenburg, J A Langendijk, J E van der Wal
Affiliations

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

W J Pattje et al. Br J Cancer. .

Abstract

Background: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5-year overall survival rate is approximately 50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer.

Methods: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy.

Results: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1-4.6; P=0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2-27.4; P=0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2-6.5; P=0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance.

Conclusion: Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC.

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Figures

Figure 1
Figure 1
Kaplan–Meier analysis for locoregional control. (A) Comparing N0 with N+ cases. (B) Comparing phosphatase and tensin homologue deleted on chromosome 10 (PTEN)− with PTEN+ cases. (C) Comparing N0 with N+/PTEN− and N+/PTEN+ cases.
Figure 2
Figure 2
(A) Clonogenic assay, comparing the radiosensitivity of Hek293 cell line stabile transfected with an empty vector or with a plasmid overexpressing phosphatase and tensin homologue deleted on chromosome 10 (PTEN). (B) Western blot analysis for PTEN, RAD51 and β-actin. Notice that overexpression of PTEN is associated with overexpression of Rad51 in the stabile transfected PTEN cell line.
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