Expression of Ki-67, cyclin D1 and apoptosis markers correlated with survival in prostate cancer patients treated by radical prostatectomy.

ABSTRACT

OBJECTIVE: The study was designed to analyse the prognostic value of proliferation markers Ki-67 and cyclin D1 and apoptosis in prostate cancer (PC) patients treated by radical prostatectomy. PATIENTS AND METHODS: Two hundred and eleven patients treated by radical prostatectomy for localised prostate cancer were clinically followed up for a mean of 7.3 years. The primary histopathological specimens were re-analysed to ensure uniform histoplthological grading and pT classification. A tissue microarray construction (TMA) was used in immunohistochemisty to assess the expression of Ki-67, cyclin D1 and the apoptosis marker Tag. The results were analysed with light microscopy and the findings were compared to standard histology, pT and clinical follow-up data. RESULTS: The co-expression of Ki-67 and cyclin Dl (p=0.05) was common. High fraction of Ki-67 positive cells and a high fraction of apoptotic cells were often present in same tumours (p=0.05). High apoptotic rate was related to positive surgical margin status (p=0.047). Low expression of Ki-67 was related to a low Gleason score (p<0.001), an absence of either capsule penetration (p = 0.029) or perineural invasion (p=0.004). High expression of cyclin Dl was related to perineural growth (p=0.039). Prostate specific antigen (PSA) recurrence-free survival (RFS) was predicted by Gleason grade (p<0.001) and capsule invasion (p=0.006). High expression of Ki-67 (p=0.03), as well as high apoptotic rate (p=0.04) were related to a high risk of cancer death. In multivariate analysis the seminal vesicle invasion was the only independent predictor of cancer death (p = 0.01). CONCLUSION: The expression of Ki-67, cyclin D1 and a high apoptotic rate are related to a malignant phenotype in prostate cancer, but their prognostic value is inferior to standard histological prognostic factors.