TY - JOUR
T1 - Ki-67 assessment of pancreatic neuroendocrine neoplasms
T2 - Systematic review and meta-analysis of manual vs. digital pathology scoring
AU - Luchini, Claudio
AU - Pantanowitz, Liron
AU - Adsay, Volkan
AU - Asa, Sylvia L
AU - Antonini, Pietro
AU - Girolami, Ilaria
AU - Veronese, Nicola
AU - Nottegar, Alessia
AU - Cingarlini, Sara
AU - Landoni, Luca
AU - Brosens, Lodewijk A
AU - Verschuur, Anna V
AU - Mattiolo, Paola
AU - Pea, Antonio
AU - Mafficini, Andrea
AU - Milella, Michele
AU - Niazi, Muhammad K
AU - Gurcan, Metin N
AU - Eccher, Albino
AU - Cree, Ian A
AU - Scarpa, Aldo
N1 - Funding Information:
This study is supported by Associazione Italiana Ricerca sul Cancro (AIRC IG n. 26343); Fondazione Cariverona: Oncology Biobank Project “Antonio Schiavi” (prot. 203885/2017); Fondazione Italiana Malattie Pancreas (FIMP-Ministero Salute J38D19000690001)
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/6
Y1 - 2022/6
N2 - Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Several challenges exist related to quantifying the Ki-67 proliferation index due to lack of method standardization and inter-reader variability. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. We systematically reviewed all published studies on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The most common advantages of DIA were improvement in the standardization and reliability of Ki-67 evaluation, as well as its speed and practicality, compared to the current gold standard approach of manual counts from captured images, which is cumbersome and time consuming. The main limitations were attributed to higher costs, lack of widespread availability (as of yet), operator qualification and training issues (if it is not done by pathologists), and most importantly, the drawback of image algorithms counting contaminating non-neoplastic cells and other signals like hemosiderin. However, solutions are rapidly developing for all of these challenging issues. A comparative meta-analysis for DIA versus manual counting shows very high concordance (global coefficient of concordance: 0.94, 95% CI: 0.83-0.98) between these two modalities. These findings support the widespread adoption of validated DIA methods for Ki-67 assessment in PanNENs, provided that measures are in place to ensure counting of only tumor cells either by software modifications or education of non-pathologist operators, as well as selection of standard regions of interest for analysis. NENs, being cellular and monotonous neoplasms, are naturally more amenable to Ki-67 assessment. However, lessons of this review may be applicable to other neoplasms where proliferation activity has become an integral part of theranostic evaluation including breast, brain, and hematolymphoid neoplasms.
AB - Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Several challenges exist related to quantifying the Ki-67 proliferation index due to lack of method standardization and inter-reader variability. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. We systematically reviewed all published studies on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The most common advantages of DIA were improvement in the standardization and reliability of Ki-67 evaluation, as well as its speed and practicality, compared to the current gold standard approach of manual counts from captured images, which is cumbersome and time consuming. The main limitations were attributed to higher costs, lack of widespread availability (as of yet), operator qualification and training issues (if it is not done by pathologists), and most importantly, the drawback of image algorithms counting contaminating non-neoplastic cells and other signals like hemosiderin. However, solutions are rapidly developing for all of these challenging issues. A comparative meta-analysis for DIA versus manual counting shows very high concordance (global coefficient of concordance: 0.94, 95% CI: 0.83-0.98) between these two modalities. These findings support the widespread adoption of validated DIA methods for Ki-67 assessment in PanNENs, provided that measures are in place to ensure counting of only tumor cells either by software modifications or education of non-pathologist operators, as well as selection of standard regions of interest for analysis. NENs, being cellular and monotonous neoplasms, are naturally more amenable to Ki-67 assessment. However, lessons of this review may be applicable to other neoplasms where proliferation activity has become an integral part of theranostic evaluation including breast, brain, and hematolymphoid neoplasms.
UR - http://www.scopus.com/inward/record.url?scp=85125620430&partnerID=8YFLogxK
U2 - 10.1038/s41379-022-01055-1
DO - 10.1038/s41379-022-01055-1
M3 - Review article
C2 - 35249100
SN - 0893-3952
VL - 35
SP - 712
EP - 720
JO - Modern Pathology
JF - Modern Pathology
IS - 6
ER -