Development and Evaluation of a Deep Learning Model for Ovarian Cancer Histotype Classification Using Whole-Slide...

The histopathological classification of ovarian carcinoma is fundamental for patient management. While microscopic evaluation by pathologists is the current diagnostic standard, it is known to be subject to interobserver variability, which can affect consistency in treatment decisions. This study addresses this clinical need by developing and validating a deep learning-based diagnostic support tool designed to enhance the objectivity and reproducibility of this classification. In this work, we address a key challenge in computational pathology-the tendency of attention mechanisms to overfit by concentrating on limited features-by systematically evaluating a direct regularization method within multiple instance learning (MIL) models. The models were trained and validated using 10-fold cross-validation on a public training set of 538 whole-slide images and further tested on an independent public dataset for the more challenging task of molecular subtype classification. We utilized features from a foundational model pre-trained on histopathology data to represent tissue morphology. Our findings demonstrate that directly regularizing the attention mechanism with a stochastic approach provides a statistically significant improvement in accuracy and generalization, highlighting its power as a robust technique to mitigate overfitting for this clinical task. In direct contrast to the reported variability in manual assessment, our final model achieved high consistency and accuracy, with a balanced accuracy of 0.854 and a Cohen's Kappa of 0.791. The model also demonstrated strong generalization on the molecular classification task. Its attention mechanism provides visual heatmaps for pathologist review, fostering interpretability and trust. We have developed a highly accurate and generalizable artificial intelligence tool that directly addresses the challenge of interobserver variability in ovarian cancer classification. Its performance highlights the potential for artificial intelligence to serve as a decision support system, standardizing histopathological assessment.