Comparison and correlation of ki67 expression and gleason score in prediction of biological behaviour of prostatic adenocarcinoma in Tanzanian patients

Abstract

Background Prostate cancer is the second most commonly diagnosed and sixth most lethal cancer in men worldwide, affecting Blacks more than Whites and Asians, with geographical variations. Not all men diagnosed with prostate cancer will develop a progressive disease; some cancers remain indolent and usually need active surveillance, while others are aggressive thus needing treatment. Gleason score is the most recognized of progression-associated prognosticators, but it misses some cases. Development of prostate cancer progression marker is anxiously awaited, to detect prostate cancer progressive cases missed by Gleason score system. Proliferation markers have been shown to be involved in progression of some human tumours. Ki67 expression contribution in predicting prostate cancer biological behaviour needs to be determined, for use in a combination to Gleason score to offer better prognosis information. Aim To compare and correlate Gleason score with Ki67 expression in predicting the biological behaviour of prostatic adenocarcinoma in Tanzanian patients, in regards to prostatic-specific antigen (PSA), stage, progression of the disease and survival duration. Methods 256 cases of prostatic adenocarcinoma diagnosed at Muhimbili National Hospital (MNH) from January 2005 to December 2006 were retrieved; 214 were retained in the study. The types of specimens were 188 (87.9%) core biopsies, 24 (11.2%) transurethral resection of prostate (TURP) and 2 cases (0.9%) of bone biopsies. A retrospective follow-up of 48 patients was done over 60 months using patients’ files; 42 excluded cases consisted of 29 cases missing tissue blocks and 13 cases without clinical data. Sections of archival tissue blocks were stained with Haematoxylin and Eosin (H&E) and MIB-1 to respectively determine Gleason score and Ki67 index by determining percent of positive cells among at least 500 cells in hotspots. Gleason score was correlated and compared to Ki67 index in terms of PSA, stage, disease progression and patient’s survival among others. Data entry and analysis were done through computer software; P value and 95% confidence interval (CI) were used as measure of variable association. Results Prostatic cancer was diagnosed in 34.73% (256/737) of prostate specimens; all cases were acinar adenocarcinoma. Mean age was 70.5 years, with the range of 42 to 96 years. Clinical data suffered poor documentation. Pre-treatment PSA levels were high, mean was 79.578 (2.32 to 500.00) ng/mL. 68.0% had advanced clinical disease, 26.1% had distant metastases. High grades predominated (Gleason score 8-10 in 34.6%, Gleason score 7 in 38.3% of cases). Median Ki67 index in prostatic adenocarcinoma was 10.39% (range 0.0% to 50.94%). 48 cases were followed up along 0.56 to 60 months (mean was 31.2 months); 2 of 15 patients were alive at last follow-up. The mean survival of fully followed-up cases was 24.50 months (95% CI=13.09 to 35.91 months). Gleason score correlated with age (P= 0.000, 95% CI=70.705 to 71.676 years), pre-treatment serum PSA level (P=0.001; 95% CI=75.45 to 84 ng/mL), average tumour extent in tissue (P= 0.000; 95% CI=66.26 to 69.49%), tumour stage (P=0.009), survival duration (P=0.029) and patient’s outcome (P=0.011). Ki67 index decreased with age (P=0.006), increased with Gleason score (P=0.001) and average tumour extent (P=0.032), correlated with disease progression (P=0.020; 95% CI= 1.163 to 6.885) and survival duration (P=0.21). Pre-treatment PSA level significantly correlated with Gleason score but not with Ki67 index; Gleason score rather than Ki67 index predicted tumour stage; both Gleason score and Ki67 index similarly predicted survival duration, but Ki67 index depicted progressive cancer disease cases missed by Gleason score system. Conclusion A combination of Gleason score and Ki67 index offers better prognostic information than either alone. The challenge to Ki67 index use is its cost and time consumption. A multicentre prospective study is recommended to confirm these findings. Standard documentation and preventive education on prostate cancer should be implemented and monitored in Tanzania.