Enhanced Breast Cancer Molecular Biomarker Classification: A Novel Two-Stage Machine Learning Pipeline for Accurate Histological Analysis of Whole Slide Images
Ahmed Aboudessouki, Khadiga Mohamed Ali, Ahmed Alksas, Mohamed Elsharkawy, Mohammed Kadhim Rahma, Mohammed Asaad Ghazal, Nagham E. Mekky, Eman M. El-Daydamony, Dikson Dibe Gondim, Ayman S El-Baz · 2025
Breast cancer, a prevalent and diverse form of cancer, is characterized by unique clinicopathologic features. Accurate classification of its molecular subtype, essential for targeted treatment and improved survival rates, relies on testing molecular biomarkers such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 antigen. This study introduces an innovative two-stage machine learning pipeline for breast cancer PR molecular biomarker classification using whole slide immunohistochemistry images. Our approach consists of two specialized stages. In the first stage, a watershed algorithm segments the Cells from the input image. Morphological and statistical features extracted from these segments are then used by machine learning classifiers to distinguish between tumor and nontumor tissues [1] –[3]. The second stage focuses on the tumor tissues that were identified in the first stage, extracting texture and appearance features to classify them into positive or negative biomarker responses, again using machine learning classifiers [4], [5]. This method not only automates the classification of PR biomarkers in tumor regions but also generates a detailed image map for each cell in the Whole Slide Image (WSI). By doing so, it can determine whether the tissue represents tumor cells and whether the tumor tissue exhibits positive or negative PR status. The results show the ability of our machine learning-based approach to augment pathologists’ diagnostic capabilities, offering significant advancements in the automated classification of histopathological images.