Expression of P53 in Benign, Premalignant and Malignant Lesions of the Gallbladder

Abstract

Background: Background: Gallbladder carcinoma is a highly aggressive cancer that is frequently preceded by benign and premalignant tumors. Identification of molecular changes associated in this development could aid in early detection and risk classification. p53, a crucial tumor suppressor gene, is frequently changed during gallbladder carcinogenesis.

Aim: To evaluate the immunohistochemical expression of p53 in benign, premalignant, and malignant lesions of the gallbladder and to assess its diagnostic and prognostic significance.

Materials and Methods:The Department of Pathology at the Integral Institute of Medical Sciences and Research in Lucknow conducted this observational cross-sectional investigation over an 18-month period. A total of 55 surgically removed gallbladder specimens were included and classified as benign (n=25), premalignant (n=16), or malignant (n=14) according to histology. P53 immunohistochemistry was conducted, and nuclear staining was evaluated semi-quantitatively. A p53 score of ≥3 was considered positive. The following statistical tests were used: Chi-square/Fisher's exact test, Kruskal-Wallis test, trend analysis, and logistic regression.

Results: p53 expression demonstrated a statistically significant progressive increase across the spectrum of lesions, from benign to premalignant and malignant categories (p < 0.001). The majority of benign lesions were p53 negative, while p53 positivity was observed in 56.3% of premalignant lesions and in all malignant lesions. Mean p53 immunoscores increased significantly with advancing lesion severity, with malignant lesions showing markedly higher scores compared to premalignant and benign lesions (p < 0.001). Although p53 positivity was strongly associated with malignant lesions and showed high diagnostic performance (AUC = 0.95), its expression pattern predominantly reflected increasing cellular atypia and tumour progression rather than serving as an absolute discriminator between benign, premalignant, and malignant lesions. These findings support the role of p53 as a useful adjunct marker, particularly in assessing lesion severity and biological behaviour.

Conclusion: p53 expression in gallbladder lesions reflects tumor progression and degree of differentiation rather than serving as a definitive diagnostic marker. Its increasing expression from benign to malignant lesions supports its role as an adjunct indicator of malignant potential when interpreted alongside histopathology.