title: Comparison of visual and automated assessment of tumour inflammatory infiltrates in patients with colorectal cancer.
abstract: BACKGROUND
  Cancer-associated inflammation is increasingly recognised to be an important determinant of oncological outcome. In colorectal cancer, the presence of peri-tumoural inflammatory/lymphocytic infiltrates predicts improved survival. To date, these infiltrates, assessed visually on haematoxylin and eosin (H&E) stained sections, have failed to enter routine clinical practice, partly due to their subjective assessment and considerable inter-observer variation. The present study aims to develop an automated scoring method to enable consistent and reproducible assessment of tumour inflammatory infiltrates in colorectal cancer.
  
  
  METHODS
  154 colorectal cancer patients who underwent curative resection were included in the study. The local inflammatory infiltrate was assessed using the method described by Klintrup-Makinen. H&E tumour sections were uploaded to an image analysis programme (Slidepath, Leica Biosystems). An image analysis algorithm was developed to count the inflammatory cells at the invasive margin. The manual and automated assessments of the tumour inflammatory infiltrates were then compared.
  
  
  RESULTS
  The automated inflammatory cell counts assessed using the freehand annotation method (p<0.001) and the rectangular box method (p<0.001) were significantly associated with both K-M score (p<0.001) and K-M grade (p<0.001). The inflammatory cell counts were divided using quartiles to group tumours with similar inflammatory cell densities. There was good agreement between the manual and automated scoring methods (intraclass correlation coefficient (ICC)=0.82). Similar to the visual K-M scoring system, the automated K-M classification of the inflammatory cell counts, using quartiles, was significantly associated with venous invasion (p<0.05) and modified Glasgow Prognostic Score (mGPS) (p⩽0.05). On univariate survival analysis, both automated K-M category (p<0.05) and automated K-M grade (p<0.005) were associated with cancer-specific survival.
  
  
  CONCLUSIONS
  The results of the present study demonstrate that automated assessment effectively recapitulates the clinical value of visual assessment of the local inflammatory cell infiltrate at the invasive margin of colorectal tumours. In addition, it is possible to obtain an objective assessment of tumour inflammatory infiltrates using routinely stained H&E sections. An automated, computer-based scoring method is therefore a workable and cost-effective approach to clinical assessment of local immune cell infiltrates in colorectal cancer.
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK.
authors: R
authors: R
authors: Forrest
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK. Electronic address: graemeguthrie@doctors.org.uk.
authors: G J K
authors: GJ
authors: Guthrie
authors: University Department of Pathology, Southern General Hospital, Glasgow, UK.
authors: C
authors: C
authors: Orange
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK.
authors: P G
authors: PG
authors: Horgan
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK.
authors: D C
authors: DC
authors: McMillan
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK.
authors: C S D
authors: CS
authors: Roxburgh
mesh_terms: D000368:Aged; D002452:Cell Count; D002469:Cell Separation / Q000379:methods; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
keywords: Automated assessment; Colorectal cancer; Tumour inflammatory cell infiltrate