R Forrest1, G J K Guthrie2, C Orange3, P G Horgan1, D C McMillan1, C S D Roxburgh1. 1. Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK. 2. Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK. Electronic address: graemeguthrie@doctors.org.uk. 3. University Department of Pathology, Southern General Hospital, Glasgow, UK.
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. CONCLUSION: 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.
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 cancerpatients 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. CONCLUSION: 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.
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