Abstract
IntroductionCyclin-D1, p53 and EGFR are molecular markers that regulate the cell cycle and play an important role in tumor progression and development. The present study evaluates the prognostic significance of these markers with chemoradiation response in patients of locally advanced oral squamous cell carcinoma (OSCC). Material and methodA total of 97 OSCC patients (females=19 and males=78), aged 20–67years and stage III/IV were recruited. Treatment response was assessed according to WHO criteria. Cyclin-D1, p53 and EGFR expressions in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei. ResultsThe positive expression rates of molecular markers were 86.6% for Cyclin-D1, 92.8% for EGFR and 85.6% for p53. The strong positive expressions of both Cyclin-D1 and p53 showed significant association with poor response. The Cox multivariate regression analysis showed coexpressions of Cyclin-D1 and p53 a significant and independent predictor of overall survival (OR=1.90, 95% CI=1.45–4.82, p=0.046) after adjusting the demographic, clinicopathological and radiological response. The strong positive expressions of Cyclin-D1 and p53 and coexpressions of Cyclin-D1, EGFR and p53 showed significant (p<0.05 or p<0.01 or p<0.001) and lower survival as compared to negative or moderate positive expressions and coexpressions, respectively. ConclusionExpressions and coexpressions of Cyclin-D1 and p53 may serve as a prognostic marker in OSCC patients.
Highlights
Cyclin-D1, p53 and EGFR are molecular markers that regulate the cell cycle and play an important role in tumor progression and development
It emanates from the fact that the clinical course of disease and treatment outcome can vary in patients with primary tumor from same site, size and stage, which would be possibly due to poor monitoring of oral squamous cell carcinoma (OSCC) in the absence of reliable biomarkers [4,5]
Various tumor markers Cyclin-D1, p53, EGFR known to be inhibitors of apoptosis play crucial roles in the initiation of intracellular signaling pathways which regulate the activation of cell proliferation, invasion, angiogenesis, metastasis and thereby influence treatment outcome [9,10,11]
Summary
Oral squamous cell carcinoma is the sixth most frequent cancer worldwide. It is a major cause of morbidity and mortality in developing nations, comprising up to 50% of all malignancies [1,2]. Various tumor markers Cyclin-D1, p53, EGFR known to be inhibitors of apoptosis play crucial roles in the initiation of intracellular signaling pathways which regulate the activation of cell proliferation, invasion, angiogenesis, metastasis and thereby influence treatment outcome [9,10,11]. Expressions of these proteins have been correlated with a more aggressive phenotype and worse prognosis; its significance in terms of clinical response and survival has already been examined in few studies and needs to be further delineated for better treatment outcome [11,12,13]. The current study is proposed to assess the combined expressions of Cyclin-D1, EGFR and p53 and its prognostic significance with treatment response in oral cancer patients undergoing chemoradiation
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