  MET protein overexpression is a targetable event in non-small cell lung
cancer (NSCLC) and is the subject of active drug development. Challenges in
identifying patients for these therapies include lack of access to validated
testing, such as standardized immunohistochemistry (IHC) assessment, and
consumption of valuable tissue for a single gene/protein assay. Development of
pre-screening algorithms using routinely available digitized hematoxylin and
eosin (H&E)-stained slides to predict MET overexpression could promote testing
for those who will benefit most. While assessment of MET expression using IHC
is currently not routinely performed in NSCLC, next-generation sequencing is
common and in some cases includes RNA expression panel testing. In this work,
we leveraged a large database of matched H&E slides and RNA expression data to
train a weakly supervised model to predict MET RNA overexpression directly from
H&E images. This model was evaluated on an independent holdout test set of 300
over-expressed and 289 normal patients, demonstrating an ROC-AUC of 0.70 (95th
percentile interval: 0.66 - 0.74) with stable performance characteristics
across different patient clinical variables and robust to synthetic noise on
the test set. These results suggest that H&E-based predictive models could be
useful to prioritize patients for confirmatory testing of MET protein or MET
gene expression status.
