Method of Tumor Pathological Micronecrosis Quantification Via Deep Learning From Label Fuzzy Proportions

Abstract

The presence of necrosis is associated with tumor progression and patient outcomes in many cancers, but existing analyses rarely adopt quantitative methods because the manual quantification of histopathological features is too expensive. We aim to accurately identify necrotic regions on hematoxylin and eosin (HE)-stained slides and to calculate the ratio of necrosis with minimal annotations on the images. An adaptive method named Learning from Label Fuzzy Proportions (LLFP) was introduced to histopathological image analysis. Two datasets of liver cancer HE slides were collected to verify the feasibility of the method by training on the internal set using cross validation and performing validation on the external set, along with ensemble learning to improve performance. The models from cross validation performed relatively stably in identifying necrosis, with a Concordance Index of the Slide Necrosis Score (CISNS) of 0.9165±0.0089 in the internal test set. The integration model improved the CISNS to 0.9341 and achieved a CISNS of 0.8278 on the external set. There were significant differences in survival (p = 0.0060) between the three groups divided according to the calculated necrosis ratio. The proposed method can build an integration model good at distinguishing necrosis and capable of clinical assistance as an automatic tool to stratify patients with different risks or as a cluster tool for the quantification of histopathological features. We presented a method effective for identifying histopathological features and suggested that the extent of necrosis, especially micronecrosis, in liver cancer is related to patient outcomes.