Study of Proliferating cell nuclear antigen expression and Angiogenesis in Urothelial neoplasms: Correlation with tumor grade and stage

Background: Urinary bladder carcinoma ranks ninth in worldwide cancer incidence. About 74,000 new cases were diagnosed in 2015 alone and 16,000 persons died of the disease. Since histopathology is considered gold standard for diagnosis, it is prudent to look for potential tumor proliferation and predictive markers in such a prevalent malignancy so as to alert surgical and medical oncologists for timely intervention and provide better patient-tailored therapy. Aims: This study is to analyze the role of potential biomarkers-proliferating cell nuclear antigen (PCNA) and angiogenesis using CD31 in urothelial neoplasms in relation to tumor grade and stage. Methods: Histopathology slides were prepared from transurethral resection of bladder tumor chips and assessed by three independent observers as per the WHO/International Society of Urologic Pathology criteria 2016. Representative sections were subjected to immunohistochemistry. PCNA labeling index (PCNA LI) and mean vessel density (MVD) were calculated. Statistical Analysis: Tests of analysis were applied as appropriate. A statistical P < 0.05 was considered significant. Results: Forty-nine patients were analyzed. PCNA LI increased with grade and stage. PCNA was significantly higher in noninvasive papillary urothelial carcinoma high grade (NIPUCHG) than in noninvasive papillary urothelial carcinoma low grade (NIPUCLG) and in infiltrating urothelial carcinoma as compared to NIPUCLG. MVD also increased with tumor grade and stage; however, a significant difference was observed only between infiltrating urothelial carcinoma and papillary urothelial neoplasm of low malignant potential. A cutoff value of 73% for PCNA and 49 vessels/high-power field for CD 31 showed 100% accuracy to differentiate between noninvasive papillary urothelial carcinoma high grade and NIPUCLG. No association was observed between tumor recurrence and PCNA or CD31 expression. Conclusion: PCNA and CD31 when used together are valuable markers to help classify urothelial neoplasms in limited tumor material. However, larger prospective studies are required for better prognostication.