PTEN as a prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck

• Published in: PloS one Vol. 7; no. 3; p. e33396
• Main Authors: Snietura, Miroslaw, Jaworska, Magdalena, Mlynarczyk-Liszka, Joanna, Goraj-Zajac, Aleksandra, Piglowski, Wojciech, Lange, Dariusz, Wozniak, Grzegorz, Nowara, Elzbieta, Suwinski, Rafal
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.03.2012; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Analysis; Angiogenesis; Biology; Biomarkers, Tumor - metabolism; Breast cancer; Cancer; Cancer therapies; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - radiotherapy; Cell survival; Chromosomes; Colorectal cancer; Combined Modality Therapy; Cyclin D1; Epidermal growth factor receptors; Evidence-based medicine; Female; Fractionation; Head; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - diagnosis; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - radiotherapy; Health aspects; Health risks; Histology; Human papillomavirus; Humans; Kinases; Larynx; Male; Medical research; Medicine; Metastasis; Middle Aged; Neoplasia; Neoplasm Grading; Neoplasms; Nucleoside-diphosphate kinase; Oncology; Oral cancer; Oral cavity; Oropharynx; p53 Protein; Paraffin; Pathology; Patients; Phosphatase; Postoperative Period; Prognosis; Prostate; Prostate cancer; PTEN Phosphohydrolase - metabolism; PTEN protein; Radiation therapy; Radiotherapy; Risk Factors; Senescence; Signal transduction; Squamous cell carcinoma; Thyroid; Thyroid cancer; Thyroid gland; Treatment Outcome; Tumor proteins; Tumor suppressor genes; Tumorigenesis; Tumors; Poland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033396

Tumor suppressor PTEN is known to control a variety of processes related to cell survival, proliferation, and growth. PTEN expression is considered as a prognostic factor in some human neoplasms like breast, prostate, and thyroid cancer. In this study we analyzed the influence of PTEN expression on the outcome of a randomized clinical trial of conventional versus 7-days-a-week postoperative radiotherapy for squamous cell cancer of the head and neck. The patients with cancer of the oral cavity, oropharynx, and larynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week (CF) or 7 days a week (p-CAIR). Out of 279 patients enrolled in the study, 147 paraffin blocks were available for an immunohistochemical assessment of PTEN. To evaluate the prognostic value of PTEN expression and the effect of fractionation relative to PTEN, the data on the outcome of a randomized clinical trial were analyzed. Tumors with a high intensity of PTEN staining had significant gain in the loco-regional control (LRC) from p-CAIR (5-year LRC 92.7% vs. 70.8%, for p-CAIR vs. CF, p = 0.016, RR = 0.26). By contrast, tumors with low intensity of PTEN did not gain from p-CAIR (5-year LRC 56.2% vs. 47.2%, p = 0.49, RR = 0.94). The intensity of PTEN highly affected the LRC in a whole group of 147 patients (5-year LRC 80.9% vs. 52.3% for high vs. low PTEN, p = 0.0007, RR = 0.32). In multivariate Cox analysis, including neck node involvement, EGFR, nm23, Ki-67, p53, cyclin D1, tumor site and margins, PTEN remained an independent predictor of LRC (RR = 2.8 p = 0.004). These results suggest that PTEN may serve as a potent prognostic and predictive marker in postoperative radiotherapy for high-risk squamous cell cancer of the head and neck.