Investigation of the Role of Vaccinia Virus VH1-Related (VHR) in Progression of Cervical Carcinoma

Abstract

Background: Vaccinia virus VH1-related (VHR) dual-specific protein phosphatase, encoded by the DUSP3 gene, has been reported to play a critical role in cell cycle progression. Recent studies have demonstrated that lack of VHR expression by cells causes their arrest in G1 and G2 phases of the cell cycle also they showed early signs of cell senescence. The usefulness of P16^INK4A in the diagnosis of cases of cervical neoplasia, has been reported in several studies. Objectives: The current study has been designed to assess the role of VHR in progression of cervical carcinoma and to evaluate the significance of P16^INK4A as a useful diagnostic biomarker; then to find any correlation between the two examined markers. Materials and Methods: In the present study, we evaluated the expression levels of VHR protein and P16^INK4A using immunohistochemistry in a series of archival formalin-fixed and paraffin-embedded tissue specimens of normal excocervix (n=10), low-grade SIL (n=12), high-grade SIL (n=18) and invasive squamous cell carcinoma (n=20). Results: VHR was expressed at very low level in the cytoplasm of parabasal cell layers of the normal cervical epithelium. VHR was significantly up-regulated in squamous intraepithelial lesions (SILs) of the cervix in LSIL (p<0.05) and HSIL (p<0.001) in comparison to normal exocervix. In cases of invasive squamous cell carcinoma, VHR was highly expressed with nuclear localization in the majority of cells compared to normal exocervix (p<0.001). The expression of p16^INK4A showed a gradual significant increase among pre-neoplastic and neoplastic cervical lesions (p<0.001). A positive correlation has been found between the expressions of the p16^INK4A and VHR (p=0.007).

Conclusion: The results suggest that VHR can be considered as a new marker for cancer progression in cervical carcinoma and a potential new target for anticancer therapy. SIL grade was positively related to the expression of p16^INK4A. Our results confirm that p16 can be a useful biomarker in the diagnosis of cervical neoplasia