Mediator of DNA damage checkpoint protein 1 (MDC1) as a prognostic marker for patients with oral squamous cell carcinoma

Abstract

Background

The mediator of DNA damage checkpoint protein 1 (MDC1) is involved in the regulation of cell cycle check points and recruitment of several repair proteins to the site of DNA double stranded breaks (DSBs). The present study aims to correlate the expression of MDC1 protein with clinicopathological parameters and to evaluate its prognostic significance in patients with oral squamous cell carcinoma (OSCC).

Methods

MDC1 protein expression was evaluated immunohistochemically from untreated 100 patients with OSCC using modified H-score method. The association of MDC1 immunostaining was evaluated with clinicopathological parameters and disease outcome using univariate and multivariate survival analysis for relapse free survival (RFS) and overall survival (OS).

Results

Incidence of nuclear and cytoplasmic expression of MDC1 protein was 85% & 92%, respectively. Strong nuclear MDC1 protein expression was found to be significantly correlated with lymphnode metastasis (p=0.032). For RFS, Kaplan-Meier survival analysis demonstrated that presence of metastatic lymphnode (p=0.001), lymphatic permeation (p=0.020) and nuclear MDC1 (p=0.005) remained significant risk predictors. In multivariate survival analysis, nuclear MDC1 (p=0.027) entered at step 2 after presence of metastatic lymphnode (p=0.002) at step 1 for predicting reduced RFS. In relation to treatment, OSCC patients exhibiting weak expression of nuclear MDC1 protein were benefited significantly when treated with surgery followed by radiation therapy (p=0.001)

Conclusion

Thus, present study showed that MDC1 protein expression could be used as a prognostic marker in predicting relapse free survival in patients with OSCC. OSCC patients expressing weak MDC1 protein could be benefited by adjuvant radiotherapy instead chemo-radiotherapy.

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