Cyclin D1 an early biomarker in oral carcinogenesis

Abstract

Background:Dysregulation of cell cycle is a fundamental hallmark of cancer progression. Cyclin D1, part of complex molecular system regulating G1-S point of cell cycle is overexpressed in variety of tumors.Aims:To look for its immunohistochemical expression in clinically normal mucosa from patients with and without tobacco habits, leukoplakia; and correlate its expression to individual atypical morphologic features, as seen in hematoxylin and eosin (H and E) sections of leukoplakia exhibiting dysplasia.Materials and Methods:We examined the expression of cyclin D1 in immunohistochemically stained sections of 15 normal buccal mucosa without any habits (group 1), 30 clinically normal mucosa from tobacco habituιs (group 2) and 30 leukoplakias exhibiting dysplasias (group 3). Descriptive statistical analysis performed. Results presented on Mean ± Standard deviation and in number (%). Adjusted Wald 95% Confidence Interval (CI) computed, percentages of morphological features assessed by Laplace estimate. Mann-Whitney U, Kruskal-Wallis test used to find the percentage expression of cyclin D1.Results:Expression of cyclin D1 in group 3 was significantly higher than in group 1 and 2 (P < 0.001, P = 0.028), expression in group 2 was significantly higher than in group 1 (P = 0.003) and were statistically significant. Generally expression of cyclin D1 was confined to lower one-third of epithelium and was highest in mild dysplasias. Among 13 atypical morphologic features, cyclin D1 expression consistently correlated with basilar hyperplasia.Conclusion:The altered pattern of cyclin D1 expression here may be an early event in conversion of normal epithelium into dysplastic epithelium and may serve as a biomarker of oral carcinogenesis. Its expression may be increased in tobacco habitués. Basilar hyperplasia should be given additional weightage in the grading system in predicting the fate of affected epithelium.

Significance of Expression of Cyclin D as an Early Indicator in Dysplastic Transformation of Oral Mucosa in Tobacco Users

“…In contrast to our results, study done by Ramakrishna A in 2013 showed 40% of normal oral mucosal samples with moderate staining but the sample size was smaller than the present study. 21 Our study showed 67% oral dysplastic lesions negative for Cyclin D which was in similarity with study done by Lam KY and colleagues in 2000 proved faint expression of Cyclin D is only limited to few high grade oral lesions and all of the OSCC cases. He further commented that this finding was because of shorter half life of Cyclin D during G1-S phase of cell cycle.…”

Modulating effect of Enicostemma littorale on the expression pattern of apoptotic, cell proliferative, inflammatory and angiogenic markers During 7, 12-Dimethylbenz (a) anthracene induced hamster buccal pouch carcinogenesis

“…The cyclin D1 expression has been correlated with histological grading in tumor staging in various types of cancers including oral carcinoma. [ 40 ] It has been pointed out that the enhanced risk of recurrence, poor prognosis and lymph nodemetastasis are associated with cyclin D1 overexpression. [ 41 ] Increase in cyclin D1 expression could cause G1 phase shortening and thereby leads to abnormal cell proliferation.…”

An update on the implications of cyclin D1 in oral carcinogenesis

“…Some authors have described this occurring in the final stages of oral carcinogenesis, close to invasion (Callender et al , ), while other researchers have described oncogenic actions of cyclin D1 during in situ carcinoma development (Califano et al , ; Forastiere et al , ; Argiris et al , ). However, the present review of the literature reveals cyclin D1 involvement throughout oral oncogenesis, including its initial phases (Castle et al , ; Sartor et al , ; Rousseau et al , ; Huang et al , ; Tsui et al , ; Ramakrishna et al , ; Mishra et al , ). This appears to be a consequence of the oncogenic activation of cyclin D1 via multiple mechanisms that act during different stages of carcinogenesis stages.…”

“…However, the oncogenic role of cyclin D1 is not limited to advanced tumor stages. Many authors found this protein to be overexpressed in potentially malignant disorders (Castle et al, 1999;Sartor et al, 1999;Rousseau et al, 2001;Huang et al, 2006b;Tsui et al, 2009;Ramakrishna et al, 2013;Mishra et al, 2015), with a tendency for higher cyclin D1 expression with each stage of oral carcinogenesis from oral dysplasia to locally advanced OSCC (Carlos de Vicente et al, 2002;Das et al, 2011;Gupta et al, 2014;Guimarães et al, 2015). Indeed, cyclin D1 overexpression was positively correlated with more advanced clinical stages of OSCC (Huang et al, 2012;Gupta et al, 2014), as corroborated by the meta-analysis of Zhao et al (Zhao et al, 2014), consistent with the correlation of this overexpression with larger tumor size and lymph node invasion.…”