p53 and ki67 as biomarkers in determining response to chemoprevention for oral leukoplakia.
BACKGROUND
We performed a randomized controlled chemoprevention trial of oral leukoplakia by administrating a low dose of beta-carotene and vitamin C supplements. 17% of subjects in the experimental arm (4/23) demonstrated clinical remission (complete or partial response) at completion of the trial. The objective of this study was to determine whether baseline expression of p53 and ki67 demonstrated any differences between those responding or not responding to our intervention. A secondary objective was to elucidate any relationship between dietary factors and clinical responses.


METHODS
For this biomarker study, we included all subjects in the experimental group (n = 23) who were non-smokers. Among 16 who completed the trial for 1 year of supplementation, there were four responders and 12 non-responders at 1-year follow-up. Following immuno-staining for p53 and ki67, the percentage of positive cell nuclei were analyzed as labeling index (LI).


RESULTS
Expression of p53 was greater in basal layers than in para-basal layers. Mean para-basal LI of p53 was higher in non-responding (26.0) than in responding subjects (11.2) (P = 0.028). ki67 LIs were not significantly different in the two groups.


CONCLUSIONS
Expression of p53 was inversely related to clinical response to the supplements. Other biomarkers that may recognize subject's responsiveness to chemoprevention require further study.
Department of Oral and Maxillofacial Surgery and Stomatology, Okazaki City Hospital, Okazaki, Japan.|Department of Oral Medicine, WHO Collaborating Centre for Oral Cancer/Precancer, King's College London, London, UK.|Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.|Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan.
Toru
T
Nagao
Department of Oral Medicine, WHO Collaborating Centre for Oral Cancer/Precancer, King's College London, London, UK.
Saman
S
Warnakulasuriya
Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
Hidenori
H
Sakuma
Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
Satoru
S
Miyabe
Department of Oral and Maxillofacial Surgery, University of Tsukuba Hospital, Ibaragi, Japan.
Shogo
S
Hasegawa
Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
Junichiro
J
Machida
Department of Public Health, Fujita Health University School of Health Science, Toyoake, Japan.
Koji
K
Suzuki
Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
Hideo
H
Fukano
Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
Kazuo
K
Shimozato
Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan.
Shuji
S
Hashimoto
D000368:Aged; D001205:Ascorbic Acid / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D007972:Leukoplakia, Oral / Q000517:prevention & control*; D008297:Male; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D019207:beta Carotene / Q000627:therapeutic use*
D015415:Biomarkers; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D019207:beta Carotene; D001205:Ascorbic Acid
beta-carotene; chemoprevention; clinical response; leukoplakia; p53