Neoplastic cell percentage estimation in tissue samples for molecular oncology: recommendations from a modified Delphi study

Kelly Dufraing, J Henricus van Krieken, Gert De Hertogh, Gerald Hoefler, Anca Oniscu, Tine P Kuhlmann, Wilko Weichert, Caterina Marchiò, Ari Ristimäki, Aleš Ryška, Jean-Yves Scoazec, Elisabeth Dequeker


AIMS: Results from external quality assessment revealed considerable variation in neoplastic cell percentages (NCP) estimation in samples for biomarker testing. As molecular biology tests require a minimal NCP, overestimations may lead to false negative test results. We aimed to develop recommendations to improve the NCP determination in a prototypical entity - colorectal carcinoma - that can be adapted for other cancer types.

METHODS AND RESULTS: A modified Delphi study was conducted to reach consensus by 10 pathologists from 10 countries with experience in determining the NCP for colorectal adenocarcinoma. This study included two online surveys and a decision-making meeting. Consensus was defined a priori as an agreement of > 80%. All pathologists completed both surveys. Consensus was reached for 8 out of 19 and 2 out of 13 questions in the first and second surveys, respectively. Remaining issues were resolved during the meeting. Twenty-four recommendations were formulated. Major recommendations resulted as follows: only pathologists should conduct the morphological evaluation; nevertheless molecular biologists/technicians may estimate the NCP, if specific training has been performed and a pathologist is available for feedback. The estimation should be determined in the area with the highest density of viable neoplastic cells and lowest density of inflammatory cells. Other recommendations concerned: the determination protocol itself, needs for micro- and macro-dissection, reporting and interpreting, referral practices and applicability to other cancer types.

CONCLUSION: We believe these recommendations may lead to more accurate NCP estimates, ensuring the correct interpretation of test results, and might help in validating digital algorithms in the future.

Original languageEnglish
Issue number3
Pages (from-to)312-319
Number of pages8
Publication statusPublished - Sep 2019


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