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March 13, 2018

Novel Method More Accurately Grades Breast Cancer Biopsies

A traditional vegetable dye-stained biopsy (left) compared to a Digistain biopsy from the same sample (right). [Imperial College London]

  • Researchers led by the department of physics and the department of surgery and cancer at Imperial College London say they have developed a novel imaging technology to grade tumor biopsies. The goals are to remove human subjectivity and ensure that patients receive the proper therapy.

    Publishing their study (“Mid-Infrared Imaging in Breast Cancer Tissue: An Objective Measure of Grading Breast Cancer Biopsies”) in Convergent Science Physical Oncology, the team described how their new method could significantly reduce the subjectivity and variability in grading the severity of cancers.

    Nearly all cancers are still diagnosed by doctors taking a biopsy, then slicing it thinly and staining it with two vegetable dyes used for more than 100 years. They look at this hematoxylin and eosin (H + E)- stained sample under a microscope and then judge the severity of the disease by eye alone. 

    Life-changing treatment decisions have to be based on this process, yet it is well known that different practitioners given the same slice will only agree on its grade about 70% of the time, resulting in an overtreatment problem, according to the Imperial College London scientists.

    “Our new Digistain technology, uses mid-infrared imaging to map the fractional concentration of nucleic acids, i.e. the nuclear-to-cytoplasmic chemical ratio (NCR) across an unstained biopsy section,” write the investigators.

    “It allows a quantitative ‘Digistain index’ (DI) score, corresponding to the NCR, to be reproducibly extracted from an objective physical measurement of a cancer. Our objective here is to evaluate its potential for aiding cancer diagnosis for the first time. We correlate the DI scores with H + E grades in a double-blind clinical pilot trial.”

    Chris Phillips, Ph.D., from the department of physics at Imperial, said: "...this study shows that [our technology] is an extremely reliable indicator of the degree of progression of the disease. Because it is based on a physical measurement, rather than a human judgment, it promises to remove the element of chance in cancer diagnosis."

    In the experiment reported in the study, the team carried out a double-blind clinical pilot trial using two adjacent slices taken from 75 breast cancer biopsies. The first slice was graded by clinicians as usual, using the standard H + E protocol. It was also used to identify the so-called region of interest (RoI), i.e., the part of the slice containing the tumor. 

    The team then used the Digistain imager to get a DI value averaged over the corresponding RoI on the other, unstained slice, and ran a statistical analysis on the results.

    "Even with this modest number of samples, the correlation we saw between the DI score and the H + E grade would only happen by chance one  time in 1400 trials,” said Dr. Phillips. “The strength of this correlation makes us extremely optimistic that Digistain will be able to eliminate subjectivity and variability in biopsy grading."

    The NCR factor that Digistain measures is known to be common to a wide range of cancers, as it occurs when the reproductive cell cycle gets disrupted in the tumor and cell nuclei get distorted with rogue DNA, he noted, pointing out that it is likely that in the long run, Digistain could help with the diagnosis of all different types of cancer.

    At a practical level, the researchers say that the Digistain imaging technology can easily and cheaply be incorporated into existing hospital labs and be used by their staff. 

    "It's easy to prove its worth by checking it with the thousands of existing biopsy specimens that are already held in hospital archives,” said Dr. Phillips. “Together these facts will smooth the path into the clinic, and it could be saving lives in only a couple of years."

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