Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential

Rosa,Eduardo  Augusto; Hurtado‑Puerto,Aura  Maria; Falcão,Denise   Pinheiro; Brietzke,Aline  Patricia; de Almeida Prado Franceschi,Luiz  Eduardo; Cavalcanti Neto,Florlorêncio   Figueiredo; Tiziane,Valdenize; Carneiro,Fabiana  Pirani; Kogawa,Evelyn  Mikaela; Moreno,Heitor; Amorim,Rivadávio  Fernandes Batista

doi:10.3892/etm.2018.5971

Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential

Authors:
- Eduardo Augusto Rosa
- Aura Maria Hurtado‑Puerto
- Denise Pinheiro Falcão
- Aline Patricia Brietzke
- Luiz Eduardo de Almeida Prado Franceschi
- Florlorêncio Figueiredo Cavalcanti Neto
- Valdenize Tiziane
- Fabiana Pirani Carneiro
- Evelyn Mikaela Kogawa
- Heitor Moreno
- Rivadávio Fernandes Batista Amorim
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Affiliations: Post‑Graduation Program in Medical Sciences, Department of Pathology, School of Medicine, University of Brasília, Brasília 70910‑900, Brazil, Laboratory for Neuropsychiatry and Neuromodulation, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA, Laboratory of Pain and Neuromodulation at Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90035‑903, Brazil, Department of Pathology, School of Medicine, University of Brasília, Brasília 70910‑900, Brazil, Center for Learning and Research, Brasília Children's Hospital, Brasília 70910‑90, Brazil, Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas, Campinas, São Paulo 13083‑970, Brazil
Published online on: March 20, 2018 https://doi.org/10.3892/etm.2018.5971
Pages: 4157-4166
Copyright: © Rosa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The association of oral lichen planus (OLP) lesions with malignant transformation risk has remained a controversial topic and is of clinical importance. Therefore, the present study evaluated the expression levels of p16, Ki‑67, budding uninhibited by benzimidazoles 3 (Bub‑3) and sex‑determining region Y‑related high mobility group box 4 (SOX4), and their roles as precancerous biomarkers in OLP. A retrospective study was performed, in which tissue blocks of OLP, oral dysplasia (OD), cutaneous lichen planus (CLP) and oral fibrous hyperplasia (OFH) were used (n=120). A positivity index (PI) for p16, BUB3, Ki‑67 and SOX4 expression was calculated in each group. The PI for p16 was 20.65% for OLP, 7.85% for OD, 86.59% for CLP and 11.8% for OFH, and the difference between these groups was statistically significant (P<0.001). PIs of Ki‑67 were indicated as 11.6% for OLP, 14.4% for OD, 8.24% for CLP and 5.5% for OFH, and a statistically significant difference was observed between the groups (P<0.001). Notably, the expression levels of BUB3 were not statistically different among groups. The highest expression levels of SOX4 were identified in CLP (P<0.001 vs. OLP/CLP; P=0,001 vs. CLP/OD). The determined expression levels of p16 and Ki‑67 suggest that specific OLP lesions may have an intermediate malignant potential and should be carefully followed up. The intense SOX4 staining in CLP indicated a different proliferation pattern of epithelium compared with oral mucosa cells. These findings suggest that SOX4 expression may also be associated with the different clinical courses of OLP and CLP.

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