Immunoexpression of p53 and p16 in Low and High-grade Serous Ovarian Cancer: A Cross-sectional Study

Abstract

Introduction: The most common malignancy of the ovary is serous carcinoma, which can be classified as either Low-grade Serous Ovarian Carcinoma (LGSOC) or High-grade Serous Ovarian Carcinoma (HGSOC) and originates from the surface epithelium. However, the overall prognosis for both cancers is very poor. Immunohistochemical analysis of p53 and p16 expression is commonly used to detect mutations. Diffuse and strong mutations (mutant type) are almost always observed in cases of HGSOC, while focal expression (wild type) suggests the absence of mutations in HGSOC. LGSOCs are characterised by a low number or absence of genetic mutations. Aim: To investigate the association between p53 and p16 expression in different grades and stages of Serous Ovarian Carcinoma (SOC). Materials and Methods: This observational cross-sectional descriptive study was conducted on 62 patients diagnosed with ovarian serous carcinoma. The study focused on examining the expressions of p53 and p16 using Immunohistochemistry (IHC) in the Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India, over a period of one and a half years (February 2021 to July 2022). The study parameters included clinical features, histological findings, staging, The Federation of Gynaecology and Obstetrics (FIGO), grading, p53 and p16 expression by IHC in all cases, and the association between p53 and p16 expression with the grade and stage of the cancer. Statistical analysis was performed using Analysis of Variance (ANOVA) and Statistical Package for Social Sciences (SPSS) software. A p-value of less than 0.05 was considered significant. Results: A total of 62 cases were included in the study, with 55 cases (88.70%) classified as LGSOC and 7 cases (11.29%) as HGSOC. The mean age for LGSOC was 53.5 years, while for HGSOC it was 54 years. Among the HGSOC cases (n=55), 45 cases (81.80%) showed diffuse positive results (mutant type) for p53. In contrast, there was no diffuse p53 expression in LGSOC cases (n=7), with 5 cases (71.40%) showing focal positivity (wild type). The p-value for comparing p53 expression in both cases was significant (<0.00001). As for p16 expression, among the HGSOC cases (n=55), 31 cases (56.40%) showed diffuse positivity (mutant type), while among the LGSOC cases (n=7), most of the cases, 5 cases (71.40%), showed focal positivity (wild type). The p-value for comparing p16 expression in both cases was significant (<0.003794). Conclusion: In conclusion, p53 along with p16 are good markers for grading SOC, and p53 is highly effective in differentiating HGSOC from LGSOC based on the positivity pattern (diffuse and strong positive for high-grade/mutant type, and focal positive for low-grade cancers). Thus, p53 has become an attractive target for the development of moleculetargeted therapies for this disease.

Keywords

• high-grade serous ovarian carcinoma
• low-grade serous ovarian carcinoma
• serous ovarian carcinoma