Visual histological assessment of morphological features reflects the underlying molecular profile in invasive breast cancer: a morphomolecular study

Rakha, Emad A.; Alsaleem, Mansour; ElSharawy, Khloud A.; Toss, Michael S.; Raafat, Sara; Mihai, Raluca; Minhas, Fayyaz A.; Green, Andrew R.; Rajpoot, Nasir M.; Dalton, Leslie W.; Mongan, Nigel P.; Rakha, Emad A.; Alsaleem, Mansour; Elsharawy, Khloud A.; Toss, Michael S.; Raafat, Sara; Mihai, Raluca; Minhas, Fayyaz A.; Green, Andrew R; Nasir, Rajpoot; Dalton, Les W.; Mongan, Nigel P

Abstract

© 2020 The Authors. Histopathology published by John Wiley & Sons Ltd Aims: Tumour genotype and phenotype are related and can predict outcome. In this study, we hypothesised that the visual assessment of breast cancer (BC) morphological features can provide valuable insight into underlying molecular profiles. Methods and results: The Cancer Genome Atlas (TCGA) BC cohort was used (n=743) and morphological features, including Nottingham grade and its components and nucleolar prominence, were assessed utilising whole-slide images (WSIs). Two independent scores were assigned, and discordant cases were utilised to represent cases with intermediate morphological features. Differentially expressed genes (DEGs) were identified for each feature, compared among concordant/discordant cases and tested for specific pathways. Concordant grading was observed in 467 of 743 (63%) of cases. Among concordant case groups, eight common DEGs (UGT8, DDC, RGR, RLBP1, SPRR1B, CXorf49B, PSAPL1 and SPRR2G) were associated with overall tumour grade and its components. These genes are related mainly to cellular proliferation, differentiation and metabolism. The number of DEGs in cases with discordant grading was larger than those identified in concordant cases. The largest number of DEGs was observed in discordant grade 1:3 cases (n=1185). DEGs were identified for each discordant component. Some DEGs were uniquely associated with well-defined specific morphological features, whereas expression/co-expression of other genes was identified across multiple features and underlined intermediate morphological features. Conclusion: Morphological features are probably related to distinct underlying molecular profiles that drive both morphology and behaviour. This study provides further evidence to support the use of image-based analysis of WSIs, including artificial intelligence algorithms, to predict tumour molecular profiles and outcome.

Citation

Alsaleem, M., Rakha, E. A., ElSharawy, K. A., Toss, M. S., Raafat, S., Mihai, R., Minhas, F. A., Green, A. R., Rajpoot, N. M., Dalton, L. W., Mongan, N. P., Rakha, E. A., Alsaleem, M., Elsharawy, K. A., Toss, M. S., Raafat, S., Mihai, R., Minhas, F. A., Green, A. R., Nasir, R., …Mongan, N. P. (2020). Visual histological assessment of morphological features reflects the underlying molecular profile in invasive breast cancer: a morphomolecular study. Histopathology, 77(4), 631-645. https://doi.org/10.1111/his.14199

• Journal Article Type: Article
• Acceptance Date: Jun 26, 2020
• Online Publication Date: Jul 2, 2020
• Publication Date: Oct 1, 2020
• Deposit Date: Jun 29, 2020
• Publicly Available Date: Jul 3, 2021
• Journal: Histopathology
• Print ISSN: 0309-0167
• Electronic ISSN: 1365-2559
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 77
• Issue: 4
• Pages: 631-645
• DOI: https://doi.org/10.1111/his.14199
• Keywords: Breast; morphology; grade; molecular profiles; digital pathology
• Public URL: https://nottingham-repository.worktribe.com/output/4737688
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/his.14199