Immunohistochemical Expression of p53 Gene and Clinicopathological Assessment of Low-grade Serous Ovarian Cancer and High-grade Serous Ovarian Cancer: A Cohort Study

Abstract

Introduction: Ovarian cancer is a significant global health concern for women. More than 85-90% of ovarian cancer cases originates from epithelial causes. Dysfunctional p53 is a hallmark of many cancers, including ovarian cancer. Alteration in functioning of p53 gene has been connected to the onset and spread of ovarian cancer. Aim: To analyse the Immunohistochemical (IHC) expression of p53 gene and clinicopathological features of Low-grade Serous Ovarian Cancer (LGSOC) and High-grade Serous Ovarian Cancer (HGSOC). Materials and Methods: This cohort study was conducted on 37 histopathologically confirmed cases of serous carcinomas of ovary in Department of Genetics, Maharshi Dayanand University, Rohtak, in collaboration with Department of Pathology, Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana, India during the period 2019 to 2023. Study was approved by the Institutional Human Ethical Research Committee (Ref no-IHEC/19/07). Parameters of study included clinical features of ovarian cancer patients, histological types, the Federation of Gynaecology and Obstetrics stage, survival of patients and prognostic factors. Analysis of p53 expression was analysed immunohistochemically. Statistical analysis was performed using GraphPad PRISM Version 8.0.1. Results: A total of 37 cases of serous carcinoma were analysed, including 26 cases of HGSOC and 11 cases of LGSOC. Comparative analysis revealed advanced-stage disease in patients HGSOC, 20 cases (76.92%) compared to 4 cases (36.36%) in LGSOC. Additionally, higher median CA125 levels were found in HGSOC patients (median 269 U/mL vs. 27 U/mL) and a higher rate of postsurgery residual disease (57.69% vs. 27.27%). Among all serous carcinoma cases, 17 cases (45.95%) showed null p53 expression, 16 cases (43.24%) showed diffuse p53 expression, and four cases (10.81%) had focal positive expression (wild type). Statistically significant differences (p-value=0.02) between the grade of serous ovarian cancer and the expression of p53 were observed. However, median Overall Survival (OS) between the two groups (39 months for HGSOC vs. 41 months for LGSOC) showed a statistically non significant difference (p-value=0.51). Log-rank statistical analysis showed a non significant association between the overall survival time of the two grades, with a Hazard Ratio of 1.384 (0.5-3.5) at 95% confidence interval with p-value=0.51. Conclusion: The significant difference in p53 IHC expression between LGSOC and HGSOC highlighted the role of p53 mutation in pathogenesis of HGSOC. However, by understanding genetic predisposition of ovarian tumour preventive steps as well as planning of early treatment can reduce the mortality rate.

Keywords

• epithelial
• genetic predisposition
• immunohistochemistry