A strategy, proposed by Perren and colleagues, to use normal tissue or stroma as a common reference providing a cut-off point for normal/dysfunctional PTEN, ensures case-to-case comparable results and was implemented in our study. The same methodology was used by Lee and co-workers, who investigated PTEN expression in patients with tongue cancer and showed that loss of PTEN is connected with shorter overall survival and event-free survival time. Furthermore, PTEN status remained an independent predictor of poor MK-2206 Abmole Die Rolle der Tight-Junction-Proteine Claudin-1, Occludin und ZO-1 in nativer und gest?rter epidermaler Wundheilung outcome when compared with tumor stage and nodal status. Similarly, the significance of PTEN expression as a marker of favourable outcome in combined modalities comprising irradiation has been reported for many other cancers, including astrocytomas, cervical and breast cancer, prostate and colorectal cancer. More ambiguous results have been shown by Tsutsui and Perez-Tonorio in the context of breast cancer. They demonstrated that prognosis more clearly depended on the combined status of PTEN/P53 and PTEN/S-phase fraction, respectively. By contrast, Pattje and colleagues recently showed that there is an increased risk of locoregional failure after postoperative radiotherapy in patients with head and neck squamous cell cancer expressing PTEN. As a proof of concept, the authors showed a decreased radiosensitivity in a human embryonic kidney cell line with an overexpressed PTEN gene. Despite the superficial similarities to the present studies, including tumor sites, treatment modality or HPV infection frequency, there are many essential differences in the experimental group and design, between our approach and the above-mentioned research. The present study was performed in a prospective clinical trial setting, ensuring strictly defined criteria of patient recruitment, uniformity of doses, and fractionation among the patients. Also, gender of individuals participating in both arms of the trial was heavily skewed toward males and correlated with tobacco smoking, as opposed to the cited paper, where both genders were distributed evenly. A different methodology of immunohistochemistry scoring is another substantial difference that could contribute to a conflicting Publications Using Abomle VE-822 result. Pattje and coworkers used a less popular, absolute method of semi-quantification, where any positive staining above background was considered as positive. This fact is of crucial importance in light of the new evidence, demonstrating that even a small decrease of PTEN activity can change the biology of the tumor and that complete loss of functionality may lead to the opposite effects, then a subtle variation in its activity.