Immunohistochemical Expression of Proliferating Cell Nuclear Antigen in Invasive Breast Carcinoma: Associations With...

Background Proliferating cell nuclear antigen (PCNA) is a nuclear protein involved in DNA replication and repair. Although PCNA is widely used experimentally as a proliferation-related marker, its clinicopathological relevance in breast carcinoma is less clearly established than that of Ki-67. This study evaluated whether increasing ordinal PCNA immunoexpression was associated with increasing histological grade. Methods This retrospective cross-sectional study identified 409 breast carcinoma cases evaluated at the Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India, from October 2018 to December 2020. The sample size was estimated to detect a correlation of 0.38 between PCNA and Ki-67, with 80% power at a two-sided alpha level of 0.05. Eligible complete-data cases were sampled using proportionate stratified random sampling according to menopausal status; computer-generated random selection without replacement yielded 26 premenopausal and 26 postmenopausal women. PCNA and Ki-67 immunoexpression were recorded as negative, mild (1+), moderate (2+), or intense (3+). The primary PCNA-grade association was evaluated using Fisher-Freeman-Halton Monte Carlo inference, Spearman correlation, the Jonckheere-Terpstra ordered-trend test, and Cramer's V; Ki-67 was a secondary comparator. Results The mean age was 49.90 ± 9.85 years, and all 52 patients were women. Grades 1, 2, and 3 comprised six (11.5%), 32 (61.5%), and 14 (26.9%) tumors, respectively. The final PCNA immunoexpression category was mild (1+) in six cases (11.5%), moderate (2+) in six cases (11.5%), and intense (3+) in 40 cases (76.9%). The 3+ PCNA immunoexpression category occurred in one of six grade 1 tumors, 25 of 32 grade 2 tumors, and all 14 grade 3 tumors. PCNA was significantly associated with grade (Fisher-Freeman-Halton Monte Carlo p<0.001; Cramer's V=0.483), with a positive monotonic relationship (Spearman rho=0.476, p<0.001) and ordered trend (Jonckheere-Terpstra Z=3.340, two-sided Monte Carlo p<0.001). PCNA also correlated with Ki-67 category (rho=0.387, p=0.005). Conclusions Increasing PCNA immunoexpression was associated with higher histological grade and showed a moderate positive ordinal association with Ki-67 in this cohort. These findings support a clinicopathological relationship between PCNA expression and proliferative morphology but do not establish independent prognostic or treatment-predictive utility. Larger prospectively assembled studies using standardized quantitative scoring and clinical follow-up are required.