Predicting transition from oral pre-malignancy to malignancy via Bcl-2 immuno-expression: Evidence and lacunae

Abstract

Bcl-2 (B cell Lymphoma −2) family comprises of both anti-apoptotic and pro-apoptotic proteins whose altered expression or change in ratio inhibits apoptosis, and promotes tumor progression. The aim of this study is to assess the usefulness of Bcl-2 in distinguishing dysplastic or malignant epithelium from non-dysplastic or normal epithelium to aid in prediction of malignant transformation potential. Material and method: Study group comprised of 30 cases of clinically diagnosed leukoplakia (OPMD), 15 cases of Oral Squamous Cell Carcinoma (OSCC) and 5 normal tissue samples. The labeling index of Bcl-2 was analyzed in immunohistochemically stained sections. Different statistical tools were used to analyze the data and to compare Bcl-2 expression qualitatively and quantitatively among all the groups. Results: An increasing trend of Bcl-2 immunoexpression was observed from normal epithelium to non-dysplastic and from non-dysplastic to dysplastic lesions. In OSCC, the peripheral cells in the differentiating epithelial islands (within the connective tissue) showed Bcl-2 immuno-reactivity, which gradually decreased towards the center. In contrast, intense and diffuse Bcl-2 immuno-reactivity was seen in poorly differentiated carcinoma. But the overall Bcl-2 positivity was less in OSCC as compared to dysplastic lesions. Conclusion: Increased expression of Bcl-2 oncoprotein in sequentially progressing epithelial dysplasia and down-regulation in differentiating carcinoma (well and moderately differentiating OSCC) unveils the clinical relevance of Bcl-2 in early stages of OSCC tumorigenesis. The heterogenous expression of Bcl-2 in carcinoma with different grades of differentiation renders them unable to be used as an independent tool for predicting transition from oral pre-malignancy to malignancy.

Keywords

• Bcl-2
• Dysplasia
• Immunohistochemistry
• Oral cancer