Expression of p16 and Galectin3 in Squamous Cell Carcinoma of Uterine Cervix, in Relation to the Histomorphological Variants: A Cross-sectional Analysis

Abstract

Introduction: Cancer of uterine cervix comprises a big chunk of cancer registration worldwide. Now-a-days the immunohistochemical marker p16 has emerged as the surrogate marker of high risk Human Papilloma Virus (HPV) infection in cervical tissue. Galectin3, a ubiquitous agent likely to modulate different pro-survival properties necessary for neoplastic cells, is recently emerging as the guardian of tumour microenvironment. Aim: To study the expression of p16 and galectin3 in different histomorphological variants of cervical Squamous Cell Carcinoma (SCC) and their association with grade and stage. Materials and Methods: An observational cross-sectional study was undertaken in the Department of Pathology in a tertiary care hospital in East India, from January, 2019 to June, 2020. Fifty three samples diagnosed as invasive Squamous Cell Carcinoma (SCC) of uterine cervix were taken by systematic random sampling. Immunohistochemical examination was done using monoclonal antibodies against p16 and galectin3 after obtaining thin sections from formalin fixed paraffin embedded blocks and retrieval of antigen. The data was interpreted by light microscopy using a semiquantitative method with respect to prefixed parameters and statistical analysis was done by chi-square test and Fisher’s exact test using SPSS version 25.0. Results: Fifty two out of fifty three cases (98.1%) of squamous cell carcinoma in this study showed almost 100% block posivity of p16 in the tumour cells -strongly corroborative with high risk HPV infection. The non-keratinizing and the basaloid variant showed the strongest intensity of staining (3+). Only one case showed complete negativity of p16 expression. In galectin3 positive cases, strong expression of this marker is found in the invasive tongues of the tumour cells at the junction of tumour stromal interface, consistent with our knowledge regarding the importance of galectin3 in regulating the tumour microenvironment. The strongest galectin3 positivity(3+) was found in the single case of Lymphoepithelioma like squamous cell carcinoma and showed almost 100% positivity among the neoplastic cell population; whereas the non-keratinizing and Basaloid variant showed almost negative expression. Significant association (p=0.00021) found between tumour grade and p16 intensity. Conclusion: The non-keratinizing and basaloid variants of squamous cell carcinoma have shown statistically significant association with highest intensity of p16 staining along with diminished expression of galectin3. Increased tumour grade is also significantly associated with strong staining intensity of p16 and decreased galectin3 expression. However, no significant association is found between galectin3 expression or intensity of p16 expression and the stage of tumour.