TY - JOUR

T1 - Neoplastic cell percentage estimation in tissue samples for molecular oncology

T2 - recommendations from a modified Delphi study

AU - Dufraing, Kelly

AU - van Krieken, J. Henricus

AU - De Hertogh, Gert

AU - Hoefler, Gerald

AU - Oniscu, Anca

AU - Kuhlmann, Tine P.

AU - Weichert, Wilko

AU - Marchiò, Caterina

AU - Ristimäki, Ari

AU - Ryška, Aleš

AU - Scoazec, Jean Yves

AU - Dequeker, Elisabeth

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - molecular biomarker testing

KW - neoplastic cell percentage

KW - recommendations

U2 - 10.1111/his.13891

DO - 10.1111/his.13891

M3 - Journal article

C2 - 31054167

AN - SCOPUS:85070664393

VL - 75

SP - 312

EP - 319

JO - Histopathology

JF - Histopathology

SN - 0309-0167

IS - 3

ER -