1. ¹Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
2. ²The Ontario Cancer Institute, University of Health Network, Toronto, ON, Canada
3. ³Department of Otolaryngology/Head and Neck Surgery, University Health Network, Toronto, ON, Canada
4. ⁴Department of Pathology, University Health Network, Toronto, ON, Canada
5. ⁵Department of Dentistry, Mount Sinai Hospital, Toronto, ON, Canada
6. ⁶Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
7. ⁷Department of Biology, York University, Toronto, ON, Canada

Correspondence: Dr G Bradley, Faculty of Dentistry, University of Toronto, 124 Edward Street, Room 511B, Toronto, ON, Canada M5G 1G6. E-mail: grace.bradley@dentistry.utoronto.ca

⁸Current address: S Tremblay is currently with Faculté de médecine dentaire, Section de stomatologie, Université Laval, Québec, Canada; C MacMillan is currently with the Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.

Revised 6 March 2007; Accepted 20 March 2007; Published online 17 April 2007.

Abstract

The Pidd (p53-induced protein with death domain) gene was shown to be induced by the tumour suppressor p53 and to mediate p53-dependent apoptosis in mouse and human cells, through interactions with components of both the mitochondrial and the death receptor signalling pathways. To study the role of Pidd in clinical tumours, we measured its expression by quantitative reverse transcription-PCR in microdissected oral squamous cell carcinomas (OSCC) with and without p53 mutation. Tumour cell apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Tumour proliferation was assessed by immunohistochemical staining for the Ki-67 antigen. We found a wide range of Pidd expression among OSCC. Statistical analysis revealed an association between Pidd expression and apoptotic index (Mann–Whitney test, P<0.001), consistent with a role of Pidd in apoptosis in this tumour type. Furthermore, we showed a positive correlation between apoptotic index and proliferative index that has not been previously described for OSCC. There was no correlation between Pidd expression and the p53 mutation status of these tumours, suggesting that Pidd expression may be regulated by p53-independent mechanisms. Further characterisation of these molecular defects in the control of proliferation and apoptosis should help in developing treatments that target OSCC according to their biological properties.