Value of Ki - 67 and p63 in Grading of Urothelial Neoplasms: An Immunohistochemical study

BACKGROUND: Bladder cancer is the ninth most common cancer in India and four times common in males than females. Over all incidences was 3.67 in males and 0.83 in females for 100,000 population. More than 90% of the bladder cancer are epithelial in origin and mostly are urothelial in type. Superficial and muscle-invasive urothelial carcinomas are two distinct types of the tumour having different biological behaviour and prognosis. More than 15% of superficial urothelial carcinoma progress to high-grade non invasive and subsequently invasive urothelial carcinoma. Detection of high-grade urothelial carcinoma is important for selection of therapy. Grading of urothelial carcinoma has prognostic significance. There is high inter observer variability in grading of urothelial neoplasms, even among the experienced pathologists. If the biopsies do not include the muscle tissue, the invasiveness of the tumour could not be assessed histopathologically. In such cases, markers which confirm the higher grade of the tumour and potential invasiveness, may be a surrogate indicator of the risk of recurrence and progression and may help in individualized therapy. Increased cellular proliferation correlates with biological aggressiveness of bladder tumours. Significant variation between Ki67 value and morphological grade of the tumour has been reported, so it might be helpful to do these marker studies to outline the individual therapy and prognosis. Expression of p63 by tumour cells indicates limited potential to progress to invasive disease and provides excellent prognosis. Impaired p63 expression characterizes the biological aggressiveness of urothelial neoplasms. MATERIALS AND METHODS: All tissue blocks of urothelial carcinoma are included in the study. Ki -67 and p63 immunohistochemistry performed in 50 cases of urothelial carcinoma. Expression of Ki -67 and p63 IHC in tumor cells are evaluated and compared with histological grade and clinical parameters. RESULTS: Decreased expression of Ki-67 was observed 80% in low grade urothelial carcinoma (16/20) whereas increased expression of Ki-67 was seen 90% in high grade urothelial carcinoma (27/30). Decreased expression of p63 was seen 95.5% (21/22) in high grade urothelial carcinoma and increased expression of p63 was seen in 64.3% (18/28) in low grade urothelial carcinoma. This result was statistically significant (p value < 0.05). CONCLUSION: The study data suggest that increased expression of Ki-67 and decreased expression of p63 is prevalent among high grade urothelial carcinoma and decreased expression of Ki-67 and increased expression of p63 is prevalent among low grade urothelial carcinoma. The increased proliferation of Ki-67 and decreased expression of p63 in low grade urothelial carcinoma cases may suggest aggressive clinical course and these cases may have increased chance of tumour recurrence and progression, so need further appropriate adjuvant treatment. Clinical trials are needed to determine the prognostic implications of these expressions