Mediator of DNA damage checkpoint protein 1 (MDC1) as a prognostic marker for patients with oral squamous cell carcinoma.
BACKGROUND
The mediator of DNA damage checkpoint protein 1 (MDC1) is involved in the regulation of cell cycle checkpoints and recruitment of several repair proteins to the site of DNA double-stranded breaks (DSBs). This study aimed 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 lymph node metastasis (P = 0.032). For RFS, Kaplan-Meier survival analysis demonstrated that presence of metastatic lymph node (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 lymph node (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).


CONCLUSIONS
Thus, this 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.
Division of Molecular Endocrinology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
Jigna Harshadbhai
JH
Dave
Division of Immunohistochemistry & Flow cytometry, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
Hemangini Hasit
HH
Vora
Division of Molecular Endocrinology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
Nandita Radhabinod
NR
Ghosh
Division of Molecular Endocrinology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
Trupti Indravadan
http://orcid.org/0000-0003-3893-9999
TI
Trivedi
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality; D018797:Cell Cycle Proteins; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D016019:Survival Analysis; D015534:Trans-Activators / Q000032:analysis*; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators
MDC1 protein expression; oral squamous cell carcinoma; prognosis; survival analysis