Automated clear cell renal carcinoma grade classification with prognostic significance

PLoS One. 2019 Oct 3;14(10):e0222641. doi: 10.1371/journal.pone.0222641. eCollection 2019.

Abstract

We developed an automated 2-tiered Fuhrman's grading system for clear cell renal cell carcinoma (ccRCC). Whole slide images (WSI) and clinical data were retrieved for 395 The Cancer Genome Atlas (TCGA) ccRCC cases. Pathologist 1 reviewed and selected regions of interests (ROIs). Nuclear segmentation was performed. Quantitative morphological, intensity, and texture features (n = 72) were extracted. Features associated with grade were identified by constructing a Lasso model using data from cases with concordant 2-tiered Fuhrman's grades between TCGA and Pathologist 1 (training set n = 235; held-out test set n = 42). Discordant cases (n = 118) were additionally reviewed by Pathologist 2. Cox proportional hazard model evaluated the prognostic efficacy of the predicted grades in an extended test set which was created by combining the test set and discordant cases (n = 160). The Lasso model consisted of 26 features and predicted grade with 84.6% sensitivity and 81.3% specificity in the test set. In the extended test set, predicted grade was significantly associated with overall survival after adjusting for age and gender (Hazard Ratio 2.05; 95% CI 1.21-3.47); manual grades were not prognostic. Future work can adapt our computational system to predict WHO/ISUP grades, and validating this system on other ccRCC cohorts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Algorithms
  • Automation
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / pathology*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / pathology*
  • Machine Learning
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis

Grants and funding

YJH is supported by the Klarman Family Foundation. KT was supported by the BIDMC High School Summer Research Program. At the time of this work, Drs. Lin and Irshad were both employees of BIDMC, and were not at commercial companies (i.e., Foundation Medicine for Lin and Figure-Eight Technologies Inc for Irshad). Those two commercial affiliations did not provide salaries for Lin and Irshad at the time of the study, and did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.