Pathomic Features Reveal Immune and Molecular Evolution From Lung Preneoplasia to Invasive Adenocarcinoma

Authors

Pingjun Chen
Frank R Rojas
Xin Hu
Alejandra Serrano
Bo Zhu
Hong Chen
Lingzhi Hong
Rukhmini Bandyoyadhyay
Muhammad Aminu
Neda Kalhor
J Jack Lee
Siba El Hussein
Joseph D Khoury
Harvey I Pass
Andre L Moreira
Vamsidhar Velcheti
Daniel H Sterman
Junya Fukuoka
Kazuhiro Tabata
Dan Su
Lisha Ying
Don L Gibbons
John V Heymach
Ignacio I Wistuba
Junya Fujimoto
Luisa M Solis Soto
Jianjun Zhang
Jia Wu

Publication Date

12-1-2023

Journal

Modern Pathology

Abstract

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials from ADC precursors. Here, we employed state-of-the-art deep learning and artificial intelligence techniques to robustly segment and recognize cells on routinely used hematoxylin and eosin histopathology images and extracted 9 biology-relevant pathomic features to decode lung preneoplasia evolution. We analyzed 3 distinct cohorts (Japan, China, and United States) covering 98 patients, 162 slides, and 669 regions of interest, including 143 normal, 129 atypical adenomatous hyperplasia, 94 AIS, 98 MIA, and 205 ADC. Extracted pathomic features revealed progressive increase of atypical epithelial cells and progressive decrease of lymphocytic cells from normal to AAH, AIS, MIA, and ADC, consistent with the results from tissue-consuming and expensive molecular/immune profiling. Furthermore, pathomics analysis manifested progressively increasing cellular intratumor heterogeneity along with the evolution from normal lung to invasive ADC. These findings demonstrated the feasibility and substantial potential of pathomics in studying lung cancer carcinogenesis directly from the low-cost routine hematoxylin and eosin staining.

Keywords

Humans, Hyperplasia, Artificial Intelligence, Eosine Yellowish-(YS), Hematoxylin, Adenocarcinoma, Lung, Lung Neoplasms, Adenocarcinoma in Situ, Precancerous Conditions, Evolution, Molecular, Carcinogenesis

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Supplementary Materials

PMID: 37678674