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Title: | Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms | Authors: | Bulloni, Matteo Sandrini, Giada Stacchiotti, Irene Barberis, Massimo Calabrese, Fiorella Carvalho, Lina Fontanini, Gabriella Alì, Greta Fortarezza, Francesco Hofman, Paul Hofman, Veronique Kern, Izidor Maiorano, Eugenio Maragliano, Roberta Marchiori, Deborah Metovic, Jasna Papotti, Mauro Pezzuto, Federica Pisa, Eleonora Remmelink, Myriam Serio, Gabriella Marzullo, Andrea Trabucco, Senia Maria Rosaria Pennella, Antonio De Palma, Angela Marulli, Giuseppe Fassina, Ambrogio Maffeis, Valeria Nesi, Gabriella Naheed, Salma Rea, Federico Ottensmeier, Christian H. Sessa, Fausto Uccella, Silvia Pelosi, Giuseppe Pattini, Linda |
Keywords: | Histopathology; Ki-67; Lung cancer; Lung neuroendocrine neoplasms; Machine learning; Prognosis; Whole-slide image | Issue Date: | 2021 | Publisher: | MDPI | Serial title, monograph or event: | Cancers | Volume: | 13 | Issue: | 19 | Abstract: | Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images. Combining features from the fields of graph theory, fractality analysis, stochastic geometry and information theory, we describe the topology of replicating cells and predict prognosis in a histology-independent way. We demonstrate how our approach outperforms the well-recognised prognostic role of Ki-67 Labelling Index on a multi-centre dataset comprising the most controversial lung NENs. Moreover, we show that our system identifies arrangement patterns in the cells positive for Ki-67 that appear independently of tumour subtyping. Strikingly, the subset of these features whose presence is also independent of the value of the Labelling Index and the density of Ki-67-positive cells prove to be especially relevant in discerning prognostic classes. These findings disclose a possible path for the future of grading and classification of NENs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | URI: | https://hdl.handle.net/10316/95902 | ISSN: | 2072-6694 | DOI: | 10.3390/cancers13194875 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
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