HistoIndex investigates the clinical utility of the unstained AI digital pathology platform in 388 patients with triple-negative breast cancer (TNBC)

TNBC is a very challenging and aggressive form of breast cancer compared to other subtypes and has a relatively poor prognosis, mainly due to lack of targeted treatment. In cancer, collagen fibers play an important role in the tumor microenvironment, remodeling the extracellular matrix (ECM). Extracellular matrix (ECM) is often rich in collagen as it becomes more “hard”. [1].. As a component of ECM, collagen can also affect the behavior of cancer cells [2]..Collagen remodeling can be seen in the interstitial compartment, especially in TNBC [3]..

Evaluation of collagen characteristics at a more detailed level

In a collaborative study involving scientists from Institute of Molecular and Cellular Biology (IMCB) To Singapore TNBC pathologists at Singapore General Hospital (SGH) scan and analyze unstained biopsies of 388 TNBC patients using HistoIndex’s AI-based SHG platform to characterize various collagens from SHG images. Was extracted in more detail.Findings published in Breast Cancer Research, a leading peer-reviewed oncology journal [3]Showed a strong correlation between some imaging functions and clinicopathological features. Collagen fiber aggregation, collagen fiber density, and dispersed fine collagen fiber length were important collagen-related parameters that were shown to have prognostic value based on patient cohorts and clinical outcomes.In addition, we analyze aggregated thick collagen (ATC) fibers and dispersed thin collagen (DTC) fibers. (As shown in Figure 1) It provided a new understanding of ongoing collagen remodeling of cancer.

Professor says Tampuaifun“The key biomarkers of TNBC are needed to stratify patients and predict clinical outcomes,” said the Chairman of the Pathology Division, Senior Consultant of the SGH Anatomical Pathology Division, and Principal Pathologist of the Study. Technological advances in pathology such as SHG assessment may improve detailed and subtle changes in important collagen features within the tumor interstitial microenvironment-collagen structure, density, length, etc. It is an important parameter that enhances the pathological assessment and allows a clearer understanding of its relationship to collagen characteristics. Tumor progression. “

Evaluation of therapeutic effect using major collagen parameters

The benefits of these new collagen parameters make the platform a valuable asset in existing and future TNBC studies currently monitoring therapeutic responses in the search for targeted therapies.For example, ongoing collaboration between HistoIndex and a team at the Memorial Sloan Kettering Cancer Center (MSK) led by a professor. Linda VerdatDr. MSK, MD, Director of Oncology and Clinical Director of Cancer Services at Norwalk Hospital, is currently investigating the effects of anti-copper therapy (copper depletion) on breast microenvironments in breast cancer patients at high risk of recurrence.

Copper is also needed to promote the growth of blood vessels that nourish dormant, later active cancer cells, and for certain cancer molecules to communicate and influence the tumor’s microenvironment. This element is then the resource needed to build a collagen scaffold that migrates as cancer cells become more aggressive. Professor Vahdat, who has spent years investigating copper depletion in TNBC studies, explains the role of copper in inducing metastasis and how when copper is withdrawn from the system, the collagen scaffold that houses the tumor is destroyed. I explained earlier [4]..

Professor Vahdat said: “Collagen in the tumor microenvironment is an unexplored predictor of treatment outcome. Preliminary data from our group suggest that copper depletion strategies can normalize the collagen microenvironment, providing a livable environment for metastasis. HistoIndex hopes to be able to predict the primary tumors that are suitable for this treatment strategy. “

About TNBC

The term triple-negative breast cancer refers to the fact that cancer cells do not have estrogen or progesterone receptors and do not overexpress a protein called HER2. A patient is diagnosed with this form of breast cancer if the cells are tested to be “negative” for all three receptors. Unlike other types of invasive breast cancer, TNBC progresses quickly, has limited targeted treatment, and generally has a poor prognosis. According to the American Cancer Society, TNBC accounts for about 10-15% of all breast cancers and is more common in African-American women under the age of 40 or women with the BRCA1 mutation. [5]..

References

1. Collagen density regulates tumor infiltrating T cell activity
   Kuczek, DE, Larsen, AMH, Horseth, ML. et al. j. Immunotherapy Cancer 7, 68 (2019). https://doi.org/10.1186/s40425-019-0556-6
2. The role of collagen in cancer: from bench to bedside
   Xu, S., Xu, H., Wang, W. et al. The role of collagen in cancer: from the bench to the bedside. J Transl Med 17, 309 (2019). https://doi.org/10.1186/s12967-019-2058-1..
3. Quantitative Stain Free Imaging and Digital Profiling of Collagen Structure Reveals Diverse Survival in Triple Negative Breast Cancer Patients
   Laurent Goal, Joe YoungJeffrey Chun Tat Rim, Kok haur ong, Haohan, Aye-aye Yongchenpo, Sydney E, Javed Iqbal, Wang Jin Hong, Burnett Lee, With Weimiao Yu Puai Huntan.. Breast Cancer Research (2020) 22:42. https://doi.org/10.1186/s13058-020-01282-x..
4. Copper depletion may reduce the recurrence of breast cancer in high-risk patients
   Website, Weil Cornell Medicine, Sandra, Edward Meyer Cancer Center.Access to December 1, 2020.. This article was first published on MDLinx.
5. Triple negative breast cancer
   The website of the American Cancer Society.Access to December 1, 2020..

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