ORIGINAL ARTICLE p53 mutations in keratocystic odontogenic tumour N. Kuroyanagi 1 , J. Machida 1 , H. Sakuma 1,2 , S. Miyabe 1,2 , O. Hashimoto 1 , M. Yokoi 3 , S. Warnakulasuriya 4 , T. Nagao 1,4,5 & K. Shimozato 1 1 Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan 2 Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 3 Department of Oral and Maxillofacial Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 4 Department of Oral Medicine and Pathology, WHO Collaborating Centre for Oral Cancer/Precancer, King’s College Dental Institute at Guy’s, King’s & St. Thomas’ Hospitals, London, UK 5 Department of Oral and Maxillofacial Surgery, Okazaki City Hospital, Okazaki, Japan Abstract Aim: The abrogation of the function for the tumour suppressor gene p53 has been suggested as one of the most common genetic alterations in neo- plasia. We evaluated p53 mutations, clinico-pathological and immunohis- tochemical findings in patients with sporadic keratocystic odontogenic tumours (KCOTs). Material and methods: A total of 32 patients with KCOT treated surgically were enrolled in this study. We performed mutation analysis of p53 using archival formalin-fixed paraffin-embedded tissue. The immunohistological technique was employed to identify TP53 expression. P53 mutations in exons 5–8 were evaluated by direct sequencing. These results were com- pared with the characteristics of each tumour. Results: Forty-four percent of the cysts showed overexpression of TP53. P53 mutations were detected in 10 cases (31.3%) of 32 KCOTs; two cases within exon 5, two cases within exon 8, five cases within exon 7 and one case in both exons 5 and 7. Five missense mutations (R248G, D247K, Q136R, V272M, V143A) and four silence mutations (138A, 158R, 247D, 279G,) were detected. P53 mutation was detected in two (50%) out of four recur- rence cases and eight (28.5%) out of 28 non-recurrence cases (P = 0.572). R248G mutation was the most common in KCOTs (15.6%). We did not detect any remarkable associations of these cases carrying p53 mutations to clinico-pathological and immunohistochemical characteristics. Conclusion: The results implied that the p53 gene alterations are involved in the development of KCOT. Key words: keratocystic odontogenic tumour, odontogenic keratocyst, p53, single-nucleotide polymorphism Correspondence to: Dr T Nagao Department of Oral and Maxillofacial Surgery Okazaki City Hospital 3-1 Goshoai Koryuji-cho Okazaki 444-8553 Aichi Japan Tel.: +81 564 66 7232 Fax: +81 564 25 5531 email: tnagao@topaz.ocn.ne.jp Accepted: 18 September 2009 doi:10.1111/j.1752-248X.2009.01048.x Clinical relevance Scientific rationale for study Keratocystic odontogenic tumour (KCOT) is a benign tumour with potential for locally destructive behaviour and high frequency of recurrence. However, molecular mechanism has not been clarified. Principal findings We performed mutation analysis of p53 gene in KCOTs, which is one of the most common tumour suppressor genes, and identified five missense mutations and four silence mutations. Practical implications Our results implied that p53 gene alteration may be involved in the development of KCOT and perhaps increases the risk in malignant transformation. P53 aberrations however, were not prognostic to predict recurrence. Oral Surgery ISSN 1752-2471 64 Oral Surgery 2 (2009) 64–70. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard