[13] Thus, immunohistochemically detectable proliferation markers could be of great value in predicting the behavior of the potentially malignant disorders and carcinomas, serving as surrogate biomarkers in cancer chemoprevention studies to evaluate possible regression scientific assays or improvement in abnormal features in the tissues of subjects at increased risk.[44] The assessment of surrogate end point biomarkers is possible because invasive carcinomas are known to be invariably preceded by potentially malignant disorders characterized by a spectrum of cellular abnormalities extending from mild dysplasia to carcinoma in situ.

[45] Nevertheless, because of the variety of methods used to assess these changes and the relatively little concern for the baseline proliferative values of the oral epithelia at different intraoral sites, numerous studies were performed to evaluate the proliferative characteristics of normal and leukoplakic epithelium using various markers of cell proliferation,[44] which have concluded that a positive balance exists between cell proliferation and cell death, which is considered to be essential for tumor growth. Wide arrays of studies have therefore determined the proliferative index (PI) in histological sections of tumors in order to determine the value of this index as a prognostic indicator.[46] A higher proliferative index was associated with a poorer prognosis in most carcinomas, with an overall increase in proliferative index with the progression from normal tissue, through dysplasia to carcinoma in cervical and oesophageal tissues.

[47,48,49] Various methods have been used to determine PI, in order to examine the possible association between epithelial proliferation and disease progression in the oral mucosa.[46] In our study, cyclin D1 was used which is the best characterized among the cyclins.[20] In view of their crucial role in cell cycle regulation and proliferation, cyclins have attracted considerable attention with regard to their putative involvement in oncogenesis. Various studies showed that cyclin D1 might be a useful prognostic factor for oral squamous cell carcinoma and also indicated that cyclin D1 might be involved in the early carcinogenesis of oral carcinoma. These data strongly supported that cyclin D1 may be involved in the initiation and development of oral squamous cell carcinoma.

Many studies were conducted to assess the cyclin D1 protein expression immunohistochemically in oral epithelial dysplasias and squamous cell carcinomas. Studies have demonstrated that abnormalities of cyclin D1 is an early event in oral neoplasia.[50] Cyclin D1 gene amplification and over-expression have been found in all grades of dysplasia and squamous cell carcinoma Anacetrapib with correlation identified between amplification and over-expression of the proteins.