Evaluation of the proliferation marker Ki-67 in a large prostatectomy cohort

• Published in: PloS one 2017-11, Vol.12 (11), p.e0186852-e0186852
• Main Authors: Richardsen, Elin, Andersen, Sigve, Al-Saad, Samer, Rakaee, Mehrdad, Nordby, Yngve, Pedersen, Mona Irene, Ness, Nora, Grindstad, Thea, Movik, Ingeborg, Dønnem, Tom, Bremnes, Roy, Busund, Lill-Tove
• Format: Article
• Language: English
• Subjects: Antigens; Biochemistry; Biological markers; Biology; Biology and Life Sciences; Biopsy; Cancer; Cancer surgery; Cancer therapies; Care and treatment; Cell cycle; Cell Proliferation; Clinical medical disciplines: 750; Cohort Studies; Digital imaging; Epithelial cells; Epithelium; Failure; Genetic aspects; Humans; Image analysis; Image processing; Ki-67 Antigen - metabolism; Klinisk medisinske fag: 750; Male; Medical disciplines: 700; Medical prognosis; Medical research; Medicine and Health Sciences; Medisinske Fag: 700; Metastasis; Methods; Multivariate Analysis; Oncology; Oncology: 762; Onkologi: 762; Pathology; Physiological aspects; Prognosis; Prostate cancer; Prostatectomy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Radiation therapy; Research and Analysis Methods; Retrospective Studies; Studies; Tumors; Urological surgery; VDP
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186852

The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation, growth and progression, and is widely used in routine clinicopathological investigation. Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to assess Ki-67 expression and related outcomes of 535 patients treated with radical prostatectomy. The percentage of tumor epithelial cells expressing Ki-67 was determined by immunohistochemical assay, both digital image analysis and visual scoring by light microscope were used for quantification. The association of Ki-67 and prostate cancer was evaluated, as well as its prognostic value. There was a positive correlation between high expression of Ki-67 and Gleason score > 7 (p < 0.001) as well as tumor size (≥ 20 mm, p = 0.03). In univariate analyses, a high expression of Ki-67 in tumor epithelium was significantly associated with biochemical failure (BF) (digital scoring, p = 0.014) and (visual scoring, p = 0.004). In the multivariate analyses, a high level of Ki-67 was an independent poor prognostic factor for biochemical failure-free survival (BFFS) (Visual scoring, Ki67, p = 0.012, HR:1.50, CI95% 1.10-2.06). In conclusion, high Ki-67 expression is an independent negative prognostic marker for biochemical failure. Our findings support the role of Ki-67 as a significant, poor prognostic factor for in prostate cancer outcome.