Prognostic value of histone H3 serine 10 phosphorylation and histone H4 lysine 12 acetylation in oral squamous cell carcinoma.

AIMS

Studies on epigenetics in oral squamous cell carcinoma (OSCC) are rare. Histone modifications comprise epigenetic mechanisms that perform a key role in gene transcription and may regulate tumour development. Thus, the aim of this study was to determine whether two post-translational histone modifications, i.e. phosphorylation of serine 10 in histone H3 and acetylation of lysine 12 in histone H4, have prognostic value for OSCC patients.

METHODS AND RESULTS

Paraffin-embedded tissue samples of 90 patients diagnosed with OSCC were obtained and subjected to immunohistochemical staining with antibodies against histone H3 with phosphorylation of serine 10 (H3S10ph) and histone H4 with acetylation of lysine 12 (H4K12ac). The associations of H3S10ph and H4K12ac expression levels with clinicopathological factors were determined. Five-year survival analysis and univariate and multivariate analyses were also performed. Both H3S10ph and H4K12ac were expressed in the nuclei of tumour cells. A low median of H3S10ph expression was significantly associated with cervical lymph node metastasis. Tumours with high H4K12ac expression were significantly associated with gender, alcohol consumption, and cervical lymph node metastasis. H4K12ac was also shown to have independent prognostic value in the multivariate analysis. Tumours with high H3S10ph expression, size >40 mm, an advanced stage and the presence of cervical lymph node metastases were associated with a better 5-year survival rate. Tumours with low H4K12ac expression, size >40 mm, an advanced stage and cervical lymph node metastasis were associated with a better 5-year survival rate.

CONCLUSIONS

These findings suggest that H3S10ph, and mainly H4K12ac, may play a role in OSCC progression and the occurrence of cervical lymph node metastasis. Also, the expression level of H4K12ac could be an independent prognostic factor for OSCC patients.