'High proliferative cribriform prostate cancer' defines a patient subgroup with an inferior prognosis

Histopathology. 2023 Dec;83(6):853-869. doi: 10.1111/his.15012. Epub 2023 Jul 28.


Aims: A cribriform pattern, reactive stroma (RS), PTEN, Ki67 and ERG are promising prognostic biomarkers in primary prostate cancer (PCa). We aim to determine the relative contribution of these factors and the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score in predicting PCa prognosis.

Methods and results: We included 475 patients who underwent radical prostatectomy (2010-12, median follow-up = 8.7 years). Cribriform pattern was identified in 57% of patients, PTEN loss in 55%, ERG expression in 51%, RS in 39% and high Ki67 in 9%. In patients with multiple samples from the same malignant focus and either PTEN loss or high Ki67, intrafocal heterogeneity for PTEN and Ki67 expression was detected in 55% and 89%, respectively. In patients with samples from two or more foci, interfocal heterogeneity was detected in 46% for PTEN and 6% for Ki67. A cribriform pattern and Ki67 were independent predictors of biochemical recurrence (BCR) and clinical recurrence (CR), whereas ERG expression was an independent predictor of CR. Besides CAPRA-S, a cribriform pattern provided the highest relative proportion of explained variation for predicting BCR (11%), and Ki67 provided the highest relative proportion of explained variation for CR (21%). In patients with a cribriform pattern, high Ki67 was associated with a higher risk of BCR [hazard ratio (HR) = 2.83, P < 0.001] and CR (HR = 4.35, P < 0.001).

Conclusions: High Ki67 in patients with a cribriform pattern identifies a patient subgroup with particularly poor prognosis, which we termed 'high proliferative cribriform prostate cancer'. These results support reporting a cribriform pattern in pathology reports, and advocate implementing Ki67.

Keywords: ERG; Ki67; PTEN; biomarker; cribriform pattern; prognosis; prostate cancer; reactive stroma.

MeSH terms

  • Biomarkers, Tumor* / metabolism
  • Humans
  • Ki-67 Antigen
  • Male
  • Neoplasm Grading
  • Prognosis
  • Prostate / pathology
  • Prostatectomy / methods
  • Prostatic Neoplasms* / pathology


  • Ki-67 Antigen
  • Biomarkers, Tumor