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UW Medicine Researchers Identify Blood Cell Genetic Mutations That Can Disrupt Liquid Biopsy Results

The discovery is yet another factor that must be considered when developing a liquid biopsy test clinical laboratories can use to detect cancer

How often do disruptive elements present in Liquid biopsies result in misdiagnoses and unhelpful drug therapies for cancer? Researchers at the University of Washington School of Medicine (UW Medicine) in Seattle wanted to know. And the results of their study provide another useful insight for pathologists about the elements that circulate in human blood which must be understood so that liquid biopsy tests can be developed that are not affected by that factor.

Based on their case series study of 69 men with advanced prostate cancer, the UW Medicine researchers determined that 10% of men have a clonal hematopoiesis of indeterminate potential (CHIP) that can “interfere” with liquid biopsies and cause incorrect reports and unneeded prostate cancer treatment, according to their paper published in the journal JAMA Oncology.

The process of clonal hematopoiesis occurs when hematopoietic stem cells generate blood cells that mimic blood mutations in the same way as hematopoiesis, Labroots explained in “Potential Problems with Liquid Biopsies.” Hence, the word “clonal” in the description. 

The UW Medicine researchers advised testing for “variants in the cell-free DNA (cfDNA)” shed in blood plasma to enable appropriate treatment for people with already diagnosed prostate cancer, noted to a UW Medicine news release.

According to pathologist Colin Pritchard, MD, PhD, Associate Professor of Laboratory Medicine and Pathology at the UW Medicine, who led the research team, “clonal hematopoiesis can interfere with liquid biopsies. For example, mutations in the genes BRCA1, BRCA2, and ATM have been closely linked to cancer development.

“Unfortunately, these same genes are also commonly mutated as a result of clonal hematopoiesis,” he told Labroots. Pritchard is also Head of the Genetics Division of Laboratory Medicine at UW Medicine, Director of Clinical Diagnostics for the Brotman Baty Institute for Precision Medicine, and Co-Director of the Genetics and Solid Tumors Laboratory at the University of Washington Medical Center.

“The good news is that, by looking at the blood cellular compartment, you can tell with pretty good certainty whether something is cancer, or something is hematopoiesis,” he said in the news release.

What Does CHIP Interference Mean to a Clinical Laboratory Blood Test?

In their published study, the UW Medicine researchers stressed the “urgent need to understand cfDNA testing performance and sources of test interferences” in light of recent US Food and Drug Administration (FDA) clearance of two PARP inhibitors (PARPi) for prostate cancer:

“We found that a strikingly high proportion of DNA repair gene variants in the plasma of patients with advanced prostate cancer are attributable to CHIP,” the researchers wrote. “The CHIP variants were strongly correlated with increased age, and even higher than expected by age group.

“The high rate of CHIP may also be influenced by prior exposure to chemotherapy,” they added. “We are concerned that CHIP interference is causing false-positive cfDNA biomarker assessments that may result in patient harm from inappropriate treatment, and delays in delivering alternative effective treatment options.

“Without performing a whole-blood control, seven of 69 patients (10%) would have been misdiagnosed and incorrectly deemed eligible for PARP-inhibitor therapy based on CHIP interference in plasma. In fact, one patient in this series had a BRCA2 CHIP clone that had been previously reported by a commercial laboratory testing company with the recommendation to use a PARPi. To mitigate these risks, cfDNA results should be compared to results from whole-blood control or tumor tissue,” the researchers concluded.

To find the clinically relevant CHIP interference in prostate cancer cfDNA testing, researchers used the UW-OncoPlex assay (developed and clinically available at UW Medicine). The assay is a multiplexed next-generation sequencing panel aimed at detecting mutations in tumor tissues in more than 350 genes, according to the UW Medicine Laboratory and Pathology website. 

“To improve cfDNA assay performance, we developed an approach that simultaneously analyzes plasma and paired whole-blood control samples. Using this paired testing approach, we sought to determine to what degree CHIP interferes with the results of prostate cancer cfDNA testing,” the researchers wrote in JAMA Oncology

Men May Receive Unhelpful Prostate Cancer Drug Therapies

The research team studied test results from 69 men with advanced prostate cancer. They analyzed patients’ plasma cfDNA and whole-blood control samples.

Tumor sequencing enabled detection of germline (cells relating to preceding cells) variants from CHIP clones.

The UW Medicine study suggested CHIP variants “accounted for almost half of the somatic (non-germline) DNA repair mutations” detected by liquid biopsy, according to the news release.

Colin Pritchard, MD, PhD
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“About half the time when the plasma is thought to contain a mutation that would guide therapy with these drugs, it actually contains CHIP variants, not prostate cancer DNA variants. That means that in about half of those tested, a patient could be told that he should be administered a drug that is not indicated to treat to his cancer,” said Colin Pritchard, MD, PhD, pathologist and Associate Professor of Laboratory Medicine and Pathology at UW Medicine in the new release. (Photo copyright: University of Washington School of Medicine.)

Other detailed findings of the UW Medicine Study:

  • CHIP variants of 2% or more were detected in cfDNA from 13 of 69 men.
  • Seven men, or 10%, having advanced prostate cancer “had CHIP variants in DNA repair genes used to determine PARPi candidacy.
  • CHIP variants rose with age: 0% in those 40 to 50; 12.5% in men 51 to 60; 6.3% in those 61 to 70; 20.8% in men 71 to 80; and 71% in men 81 to 90.
  • Whole-blood control made it possible to distinguish prostate cancer variants from CHIP interference variants.

“Men with prostate cancer are at high risk of being misdiagnosed as being eligible for PARPi therapy using current cfDNA tests; assays should use a whole-blood control sample to distinguish CHIP variants from prostate cancer,” the researchers wrote in JAMA Oncology.

Liquid Biopsies Are ‘Here to Stay’

Surgical oncologist William Cance, MD, Chief Medical and Scientific Officer, American Cancer Society (ACS) in Atlanta, recognizes the challenge of tumor biology to liquid biopsies. 

“Genetic abnormalities are only one piece of the puzzle. We need to look comprehensively at tumors for the best therapy, from their metabolic changes and protein signatures in the blood to the epigenetic modifications that may occur, as cancers take hold,” he told Oncology Times. “It’s not just shed DNA in the blood.”

The UW Medicine study demonstrates the importance of understanding how all elements in liquid biopsies interact to affect clinical laboratory test results.

“I think liquid biopsies are here to stay,” Cance told Oncology Times. “They’re all part of precision medicine, tailored to the individual.”

Donna Marie Pocius

Related Information:

Association of Clonal Hematopoiesis in DNA Repair Genes with Prostate Cancer Plasma Cell-free DNA Testing Interference

Potential Problems with Liquid Biopsies

Blood Cell Mutations Confound Prostate Cancer Liquid Biopsy

Pursing and Perfecting Use of Liquid Biopsies in Cancer Early Detection

Researchers at Harvard’s Massachusetts General Hospital Develop a Non-Invasive Liquid Biopsy Blood Test to Detect and Monitor Common Brain Tumors in Adults

Using Extracellular Vesicles, Researchers Highlight Viability of Liquid Biopsies for Cancer Biomarker Detection in Clinical Laboratories

New studies in UK and at Stanford University Show Lung Cancer Cells Circulating in Blood; Findings Could Make It Possible for Pathologists to Diagnose Cancer with ‘Liquid Biopsies’

Attention All Surgical Pathologists: Algorithms for Automated Primary Diagnosis of Digital Pathology Images Likely to Gain Regulatory Clearance in Near Future

Hello primary diagnosis of digital pathology images via artificial intelligence! Goodbye light microscopes!

Digital pathology is poised to take a great leap forward. Within as few as 12 months, image analysis algorithms may gain regulatory clearance in the United States for use in primary diagnosis of whole-slide images (WSIs) for certain types of cancer. Such a development will be a true revolution in surgical pathology and would signal the beginning of the end of the light microscope era.

A harbinger of this new age of digital pathology and automated image analysis is a press release issued last week by Ibex Medical Analytics of Tel Aviv, Israel. The company announced that its Galen artificial intelligence (AI)-powered platform for use in the primary diagnosis of specific cancers will undergo an accelerated review by the Food and Drug Administration (FDA).

FDA’s ‘Breakthrough Device Designation’ for Pathology AI Platform

Ibex stated that “The FDA’s Breakthrough Device Designation is granted to technologies that have the potential to provide more effective treatment or diagnosis of life-threatening diseases, such as cancer. The designation enables close collaboration with, and expedited review by, the FDA, and provides formal acknowledgement of the Galen platform’s utility and potential benefit as well as the robustness of Ibex’s clinical program.”

“All surgical pathologists should recognize that, once the FDA begins to review and clear algorithms capable of using digital pathology images to make an accurate primary diagnosis of cancer, their daily work routines will be forever changed,” stated Robert L. Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report. “Essentially, as FDA clearance is for use in clinical care, pathology image analysis algorithms powered by AI will put anatomic pathology on the road to total automation.

“Clinical laboratories have seen the same dynamic, with CBCs (complete blood counts) being a prime example. Through the 1970s, clinical laboratories employed substantial numbers of hematechnologists [hematechs],” he continued. “Hematechs used a light microscope to look at a smear of whole blood that was on a glass slide with a grid. The hematechs would manually count and record the number of red and white blood cells.

“That changed when in vitro diagnostics (IVD) manufacturers used the Coulter Principle and the Coulter Counter to automate counting the red and white blood cells in a sample, along with automatically calculating the differentials,” Michel explained. “Today, only clinical lab old-timers remember hematechs. Yet, the automation of CBCs eventually created more employment for medical technologists (MTs). That’s because the automated instruments needed to be operated by someone trained to understand the science and medicine involved in performing the assay.”

Primary Diagnosis of Cancer with an AI-Powered Algorithm

Surgical pathology is poised to go down a similar path. Use of a light microscope to conduct a manual review of glass slides will be supplanted by use of digital pathology images and the coming next generation of image analysis algorithms. Whether these algorithms are called machine learning, computational pathology, or artificial intelligence, the outcome is the same—eventually these algorithms will make an accurate primary diagnosis from a digital image, with comparable quality to a trained anatomic pathologist.

How much of a threat is automated analysis of digital pathology images? Computer scientist/engineer Ajit Singh, PhD, a partner at Artiman Ventures and an authority on digital pathology, believes that artificial intelligence is at the stage where it can be used for primary diagnosis for two types of common cancer: One is prostate cancer, and the other is dermatology.

Ajit Singh, PhD speaking at the Executive War College

On June 17, Ajit Singh, PhD (above), Partner at Artiman Ventures, will lead a special webinar and roundtable discussion for all surgical pathologists and their practice administrators on the coming arrival of artificial intelligence-powered algorithms to aid in the primary diagnosis of certain cancers. Regulatory approval for such solutions may happen by the end of this year. Such a development would accelerate the transition from light microscopes to a fully digital pathology workflow. Singh is shown above addressing the 2018 Executive War College. (Photo copyright: The Dark Report.)

“This is particularly true of prostate cancer, which has far fewer variables compared to breast cancer,” stated Singh in an interview published by The Dark Report in April. (See TDR, “Is Artificial Intelligence Ready for First Use in Anatomic Pathology?” April 12, 2021.)

“It is now possible to do a secondary read, and even a first read, in prostate cancer with an AI system alone. In cases where there may be uncertainty, a pathologist can review the images. Now, this is specifically for prostate cancer, and I think this is a tremendous positive development for diagnostic pathways,” he added.

Use of Digital Pathology with AI-Algorithms Changes Diagnostics

Pathologists who are wedded to their light microscopes will want to pay attention to the impending arrival of a fully digital pathology system, where glass slides are converted to whole-slide images and then digitized. From that point, the surgical pathologist becomes the coach and quarterback of an individual patient’s case. The pathologist guides the AI-powered image analysis algorithms. Based on the results, the pathologist then orders supplementary tests appropriate to developing a robust diagnosis and guiding therapeutic decisions for that patient’s cancer.

In his interview with The Dark Report, Singh explained that the first effective AI-powered algorithms in digital pathology will be developed for prostate cancer and skin cancer. Both types of cancer are much less complex than, say, breast cancer. Moreover, the AI developers have decades of prostate cancer and melanoma cases where the biopsies, diagnoses, and downstream patient outcomes create a rich data base from which the algorithms can be trained and tuned.

To help surgical pathologists, pathologist-business leaders, and pathology group practice administrators understand the rapid developments in AI-powered digital pathology analysis, Dark Daily is conducting “Clinical-Grade Artificial Intelligence (AI) for Your Pathology Lab: What’s Ready Now, What’s Coming Soon, and How Pathologists Can Profit from Its Use,” on Thursday, June 17, 2021, from 1:00 PM to 2:30 PM EDT.

This webinar is organized as a roundtable discussion so participants can interact with the expert panelists. The Chair and Moderator is Ajit Singh, PhD, Adjunct Professor at the Stanford School of Medicine and Partner at Artiman Ventures.

Panelists for June 17 webinar, Clinical-Grade Artificial Intelligence (AI) for Your Pathology Lab: What’s Ready Now, What’s Coming Soon, and How Pathologists Can Profit from Its Use

The panelists (above) represent academic pathology, community hospital pathology, and the commercial sector. They are:

Because the arrival of automated analysis of digital pathology images will transform the daily routine of every surgical pathologist, it would be beneficial for all pathology groups to have one or more of their pathologists register and participate in this critical webinar.

The roundtable discussion will help them understand how quickly AI-powered image analysis is expected be cleared for use by the FDA in such diseases as prostate cancer and melanomas. Both types of cancers generate high volumes of case referrals to the nation’s pathologists, so potential for disruption to long-standing client relationships, and the possible loss of revenue for pathology groups that delay their adoption of digital pathology, can be significant.

On the flip side, community pathology groups that jump on the digital pathology bandwagon early and with the right preparation will be positioned to build stronger client relationships, increase subspecialty case referrals, and generate additional streams of revenue that boost partner compensation within their group.

Act now to guarantee your place at this important webinar. Click HERE to register, or copy and paste the URL https://www.darkdaily.com/webinar/clinical-grade-artificial-intelligence-for-your-pathology-lab/ into your browser.

Also, because so many pathologists are working remotely, Dark Daily has arranged special group rates for pathology practices that would like their surgical pathologists to participate in this important webinar and roundtable discussion on AI-powered primary diagnosis of pathology images. Inquire at info@darkreport.com or call 512-264-7103.

—Michael McBride

Related Information:

Ibex Granted FDA Breakthrough Device Designation: Ibex’s Galen AI-powered platform is recognized by the FDA as breakthrough technology with the potential to more effectively diagnose cancer

Is Artificial Intelligence Ready for First Use in Anatomic Pathology?

University of East Anglia Researchers Develop Non-Invasive Prostate Cancer Urine Test

The researchers believe their test ‘could reduce the number of unnecessary prostate cancer biopsies by 32%,’ UEA reported

New diagnostic technologies may make it possible for men to provide a urine sample that can allow a clinical laboratory to not only accurately diagnose prostate cancer but also help determine whether it is an aggressive form of prostate cancer. Researchers in the United Kingdom (UK) recently described just such a test in an online, peer-reviewed journal.

Development of a non-invasive method of diagnosing prostate cancer would be significant for anatomic pathologists in the United States. In the US alone, approximately 248,000 men will be diagnosed with this type of cancer in 2021. Prostate biopsies represent a major proportion of case referrals to community pathology groups.

Moreover, were such a non-invasive test for prostate cancer also able to identify those individuals with fast-growing prostate cancers, that would help urologists make more informed treatment decisions.

A Disease Men More Commonly Die ‘With’ Rather than ‘From’

According to CDC statistics, most men over the age of 80 will have some form of slow-growing prostate cancer when they die. However, a percentage of men each year contract a rapidly growing aggressive form of the cancer, and until recently, diagnosing which cancer a patient was fighting often required multiple invasive prostate needle biopsies. But that may soon change.

Researchers at the University of East Anglia (UEA) Norwich Medical School in the United Kingdom (UK) have developed a non-invasive urine test for prostate cancer that they say also can determine the aggressiveness of the disease. Knowing this may help physicians better assess a patient’s risk prior to ordering invasive needle biopsies, a UEA article notes.

The UEA test may also allow for self-collection of the biological sample, and if it proves accurate, the test could bring additional revenue to clinical laboratories that would perform the urine testing.

The UEA researchers published their study in the peer-reviewed open-access journal Cancers, titled, “Integration of Urinary EN2 Protein and Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy.”

“In this work we develop a test that predicts whether a patient has prostate cancer and how aggressive the disease is from a urine sample. This model combines the measurement of a protein-marker called EN2 and the levels of 10 genes measured in urine and proves that integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy,” they wrote.

“While prostate cancer is responsible for a large proportion of all male cancer deaths, it is more commonly a disease men die with rather than from,” said Daniel Brewer, PhD, one of the lead researchers on this study. “Therefore, there is a desperate need for improvements in diagnosing and predicting outcomes for prostate cancer patients to minimize over-diagnosis and overtreatment whilst appropriately treating men with aggressive disease, especially if this can be done without taking an invasive biopsy.

“Invasive biopsies come at considerable economic, psychological, and societal cost to patients and healthcare systems alike,” he added. Brewer is Senior Lecturer in Cancer Bioinformatics and a group leader within the Cancer Genetics Team at UEA’s Norwich Medical School.

Daniel-Brewer-PhD

“Our new urine test not only shows whether a patient has prostate cancer, but it importantly shows how aggressive the disease is. This allows patients and doctors to select the correct treatment,” said Daniel Brewer, PhD (above), Senior Lecturer and Lead Researcher, UEA Norwich Medical School, in the news release. (Photo copyright: Eastern Daily Press.)

Possibility of Reducing Needle Biopsies by 32%

Called “ExoGrail,” the UEA’s new test builds on their earlier development of the Prostate Urine Risk (PUR) and ExoMeth tests. The test works by integrating two biomarkers.

  • Measurements of EN2, a protein-marker, and
  • Levels of gene expression of 10 genes related to prostate cancer.

The researchers tested ExoGrail on urine samples from 207 patients at Norfolk and Norwich University Hospital (NNUH) who also had needle biopsy samples available.

According to the published study, the UEA ExoGrail urine test enabled:

  • Results comparable to the biopsy findings.
  • Identification of people with prostate cancer and people without it.
  • Risk scoring that noted aggressive prostate cancer and need for biopsy.
  • Potential to reduce unnecessary biopsies by 32%.

“ExoGrail resulted in accurate predictions even when serum PSA [protein-specific antigen] levels alone proved inaccurate; patients with a raised PSA but negative biopsy result possessed ExoGrail scores significantly different from both clinically benign patients and those with low-grade Gleason 6 disease, whilst still able to discriminate between more clinically significant Gleason ≥ 7 cancers,” the researchers stated in their published study.

“The adoption of ExoGrail into current clinical pathways for reducing unnecessary biopsies was considered, showing the potential for up to 32% of patients to safely forgo an invasive biopsy without incurring excessive risk,” they noted.

Prostate Cancer Patients May Soon Have Options

While more research is needed, the new UEA Norwich Medical School ExoGrail test introduces compelling non-invasive methods for diagnosing prostate cancer. Patients with findings of aggressive cancer can proceed to biopsies, while others determined to have non-aggressive forms of prostate cancer may be able to avoid more invasive tests and the associated costs and stress.

Additionally, men may soon be able to collect their own specimens without the need to visit the primary care doctor or a patient service center.

A follow-up study underway at the University of East Anglia and the NNUH involves sending 2,000 men in the UK, Europe, and Canada home testing “prostate screening boxes” to “to collect men’s urine samples at-home,” according to a UEA new release, which noted that “the Prostate Screening Box has been developed in collaboration with REAL Digital International Limited to create a kit that fits through a standard letterbox.”

“We have developed the PUR (Prostate Urine Risk) test, which looks at gene expression in urine samples and provides vital information about whether a cancer is aggressive or ‘low risk,’” said Jeremy Clark, PhD, Senior Research Associate at UEA’s Norwich Medical School.

“The Prostate Screening Box part sounds like quite a small innovation, but it means that in future the monitoring of cancer in men could be so much less stressful for them and reduce the number of expensive trips to the hospital,” he added.

Anatomic pathologists and clinical laboratory managers will want to follow the progress of these clinical studies. A non-invasive, urine-based test for prostate cancer could be a game-changer if it can detect prostate cancer with comparable accuracy to the tissue-based diagnostics that are the current standard of care in the diagnosis of prostate cancer.

—Donna Marie Pocius

Related Information:

Integration of Urinary EN2 Protein and Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy

New Prostate Cancer Urine Test Shows How Aggressive Disease Is and Could Reduce Invasive Biopsies

Tests to Diagnose and Stage Prostate Cancer

Prostate Cancer Key Statistics

UEA Researchers Develop Prostate Cancer Test That Could Reduce Biopsies

Thousands of Men to Trial Prostate Cancer Home Testing Kit

UPMC Researchers Develop Artificial Intelligence Algorithm That Detects Prostate Cancer with ‘Near Perfect Accuracy’ in Effort to Improve How Pathologists Diagnose Cancer

Working from tissue slides similar to those used by surgical pathologists, the algorithm accurately detects prostate cancer with an impressive 98% sensitivity

It could be that a new milestone has been reached on the road to using artificial intelligence (AI) to help anatomic pathologists diagnose cancer and other diseases. A research collaboration between a major American university and an Israeli company recently published a study about the ability of an AI algorithm to correctly diagnose prostate cancer.

The collaboration involved researchers at the University of Pittsburgh Medical Center (UPMC) and at Ibex Medical Analytics of Israel. The research team created an AI algorithm dubbed the Galen Prostate (part of the Galen Platform). In the study, the Galen Prostate AI accurately detected prostate cancer with 98% sensitivity and 97% specificity.

Researchers noted that this level of diagnostic sensitivity and specificity was significantly higher, compared to previously tested cancer-detecting algorithms that utilized tissue slides. The UPMC scientists published their findings in The Lancet Digital Health, titled, “An Artificial Intelligence Algorithm for Prostate Cancer Diagnosis in Whole Slide Images of Core Needle Biopsies: A Blinded Clinical Validation and Deployment Study.”

AI Show and Tell in Anatomic Pathology

The scientists trained the Galen Prostate AI to recognize prostate cancer by having it examine images from over a million parts of stained tissue slides taken from patient biopsies. Expert pathologists labeled each image to teach the algorithm how to distinguish between healthy and abnormal tissue. The AI was then tested on 1,600 different tissue slide images that had been collected from 100 patients seen at UPMC who were suspected of having prostate cancer.  

“Humans are good at recognizing anomalies, but they have their own biases or past experience,” said Rajiv Dhir, MD, Chief Pathologist and Vice Chair of Pathology at UPMC Shadyside Hospital, Professor of Biomedical Informatics at University of Pittsburgh, and senior author of the study, in a UPMC news release. “Machines are detached from the whole story. There’s definitely an element of standardizing care.”

Ibex Galen Prostate AI solution
The image above is “of prostate cancer (represented by the heatmap) detected by the Ibex Galen Prostate [AI] solution on a biopsy that was previously diagnosed as benign by the pathologist,” stated an Ibex news release announcing the UPMC study. (Photo copyright: Ibex.)

UPMC Algorithm Goes Beyond Cancer Detection, Exceeds Human Pathologists

The researchers also noted that this is the first algorithm to extend beyond cancer detection. It reported high performance for tumor grading, sizing, and invasion of surrounding nerves—clinically important features of pathology reports.  

“Algorithms like this are especially useful in lesions that are atypical,” Dhir said. “A nonspecialized person may not be able to make the correct assessment. That’s a major advantage of this kind of system.”

The algorithm also flagged six slides as potentially containing abnormal tissue that were not flagged by human pathologists. However, the researchers pointed out that this difference does not mean the AI is better than humans at detecting prostate cancer. It is probable, for example, that the pathologists simply saw enough evidence of malignancy elsewhere in the patients’ samples to recommend treatment.

Other Studies Where AI Detected Prostate Cancer

The UPMC researchers are not the first to use AI to detect prostate cancer. In February, The Lancet Oncology published a study from researchers at Radboud University Medical Center (RUMC) in the Netherlands who developed a deep learning AI system that could determine the aggressiveness of prostate cancer in certain patients. 

For that research, the RUMC scientists collected 6,000 biopsies from more than 1,200 men. They then showed the biopsy images along with the original pathology reports to their AI system. Using deep learning, the AI was able to detect and grade prostate cancer according to the Gleason Grading System (aka, Gleason Score), which is used to rate prostate cancer and choose appropriate treatment options. The Gleason Score ranges from one to five and most cancers obtain a score of three or higher. 

“Systems such as ours can be used in different ways. First, it can be used to screen biopsies and to filter out the easy (benign) cases. This could reduce the workload for pathologists,” said Wouter Bulten, a PhD candidate at Radboud who worked on the study, in an interview with HemOnc Today. “Second, the system can be used as a second opinion after the pathologist’s initial read. The system can flag a case if its opinion differs from that of the pathologist. It also can give feedback during the first read, showing the pathologist where to look. In this case, the pathologist needs only to confirm the opinion of the AI system.” 

Can Today’s AI Outperform Human Pathologists?

In their research, the Radboud team discovered that their AI system was able to achieve pathologist-level performance and, in some cases, even performed better than human pathologists. However, they do not foresee AI replacing the need for pathologists, but rather emerging as another method to use in cancer detection and treatment.  

“We see our system as an additional tool that the pathologist can use. Although our system performs very well, it still makes mistakes,” stated Bulten. “These mistakes are often different from those a human would make. We believe that when you merge the expertise of the pathologist with the second opinion of an AI system, you get the best of both worlds.” 

According to the American Cancer Society, prostate cancer is the second most common cancer among men in the US, after skin cancer. The organization estimates there will be approximately 191,930 new cases of prostate cancer diagnosed and about 33,330 deaths from the disease in the US in 2020. 

Though the UPMC study focused only on prostate cancer, the scientists believe their algorithm can be trained to detect other types of cancer as well. AI in clinical diagnostics is clearly progressing, however more studies will be required. Nevertheless, if AI can truly become a useful tool for anatomic pathologists to detect cancer earlier, we may see a welcomed reduction in cancer deaths.   

—JP Schlingman

Related Information:

Newly Developed AI Capable of Identifying Prostate Cancer with “Near-perfect Accuracy”

An Artificial Intelligence Algorithm for Prostate Cancer Diagnosis in Whole Slide Images of Core Needle Biopsies: A Blinded Clinical Validation and Deployment Study

Artificial Intelligence Identifies Prostate Cancer

The Lancet Reports Outstanding Performance of Ibex Medical Analytics’ AI-based Algorithm in a Study at UPMC

Prostate Cancer Can Now be Diagnosed Better Using Artificial Intelligence

AI System Outperforms Pathologists in Identifying Prostate Cancer Aggressiveness

Automated Deep-learning System for Gleason Grading of Prostate Cancer using Biopsies: A Diagnostic Study

New AI Technology Helps Pathologists Spot Cancer

Hospitals Worldwide Are Deploying Artificial Intelligence and Predictive Analytics Systems for Early Detection of Sepsis in a Trend That Could Help Clinical Laboratories, Microbiologists

CMS Considers Using Artificial Intelligence to Battle Fraud; Medical Laboratories Must Ensure Billing Practices Comply with New Federal Affiliation Regulations

Mobile Device Software Companies Are Developing Smartphone Apps That Use Artificial Intelligence to Test for COVID-19, Potentially Bypassing the Clinical Laboratory Altogether

University of Queensland Researches May Have Found a Universal Biomarker That Identifies Cancer in Various Human Cells in Just 10 Minutes!

This research could lead to a useful liquid biopsy test that would be a powerful new tool for clinical laboratories and anatomic pathologists

Cancer researchers have long sought the Holy Grail of diagnostics—a single biomarker that can quickly detect cancer from blood or biopsied tissue. Now, researchers in Australia may have found that treasure. And the preliminary diagnostic test they have developed reportedly can return results in just 10 minutes with 90% accuracy.

In a news release, University of Queensland researchers discussed identifying a “simple signature” that was common to all forms of cancer, but which would stand out among healthy cells. This development will be of interest to both surgical pathologists and clinical laboratory managers. Many researchers looking for cancer markers in blood are using the term “liquid biopsies” to describe assays they hope to develop which would be less invasive than a tissue biopsy.

“This unique nano-scaled DNA signature appeared in every type of breast cancer we examined, and in other forms of cancer including prostate, colorectal, and lymphoma,” said Abu Sina, PhD, Postdoctoral Research Fellow at the Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), in the news release.

“We designed a simple test using gold nanoparticles that instantly change color to determine if the three-dimensional nanostructures of cancer DNA are present,’ said Matt Trau, PhD, Professor of Chemistry at the University of Queensland, and Deputy Director and Co-Founder of UQ’s AIBN, in the news release.

The team’s test is preliminary, and more research is needed before it will be ready for Australia’s histopathology laboratories (anatomic pathology labs in the US). Still, UQ’s research is the latest example of how increased knowledge of DNA is making it possible for researchers to identify new biomarkers for cancer and other diseases.

“We certainly don’t know yet whether it’s the holy grail for all cancer diagnostics, but it looks really interesting as an incredibly simple universal marker of cancer, and as an accessible and inexpensive technology that doesn’t require complicated lab-based equipment like DNA sequencing,” Trau added.

Such a diagnostic test would be a boon to clinical laboratories and anatomic pathology groups involved in cancer diagnosis and the development of precision medicine treatments.

One Test, 90% Accuracy, Many Cancers

The UQ researchers published their study in the journal Nature Communications. In it, they noted that “Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as ‘Methylscape’ is displayed by most cancer types, thus may serve as a universal cancer biomarker.”

While methyl patterning is not new, the UQ researchers say they were the first to note the effects of methyl pattern in a particular solution—water. With the aid of transmission electron microscopy, the scientists saw DNA fragments in three-dimensional structures in the water. But they did not observe the signature in normal tissues in water.

Methylation are marks that indicate whether pieces of DNA should be read,” Dino DiCarlo, PhD, Professor in the Department of Bioengineering and Biomedical Engineering, University of California Los Angeles (UCLA) and Director of Cancer Nanotechnology at UCLA’s Jonsson Comprehensive Cancer Center, told USA Today.


“To date, most research has focused on the biological consequences of DNA Methylscape changes, whereas its impact on DNA physicochemical properties remains unexplored,” UQ scientists Matt Trau, PhD (left), Abu Sina, PhD (center), and Laura Carrascosa (right), wrote in their study. “We exploit these Methylscape differences to develop simple, highly sensitive, and selective electrochemical or colorimetric one-step assays for the detection of cancer.” (Photo copyright: University of Queensland.)

Their test averaged 90% accuracy during the testing of 200 human cancer samples. Furthermore, the researchers found the DNA structure to be the same in breast, prostate, and bowel cancers, as well as lymphomas, noted The Conversation.

“We find that DNA polymeric behavior is strongly affected by differential patterning of methylcytosine leading to fundamental differences in DNA solvation and DNA-gold affinity between cancerous and normal genomes,” the researchers wrote in NatureCommunications.“We exploit these methylscape differences to develop simple, highly sensitive, and selective electrochemical or one-step assays for detection of cancer.”

Next Steps for the “Gold Test”

“This approach represents an exciting step forward in detecting tumor DNA in blood samples and opens up the possibility of a generalized blood-based test to detect cancer, Ged Brady, PhD, Cancer Research UK Manchester Institute, told The Oxford Scientist. “Further clinical studies are required to evaluate the full clinic potential of the method.”

Researchers said the next step is a larger clinical study to explore just how fast cancer can be detected. They expressed interest in finding different cancers in body fluids and at various stages. Another opportunity they envision is to use the cancer assay with a mobile device.

DiCarlo told USA Today that such a mobile test could be helpful to clinicians needing fast answers for people in rural areas. However, he’s also concerned about false positives. “You don’t expect all tumors to have the same methylation pattern because there’s so many different ways that cancer can develop,” he told USA Today. “There are some pieces that don’t exactly align logically.”

The UQ researchers have produced an intriguing study that differs from other liquid biopsy papers covered by Dark Daily. While their test may need to be used in combination with other diagnostic tests—MRI, mammography, etc.—it has the potential to one day be used by clinical laboratories to quickly reveal diverse types of cancers.  

—Donna Marie Pocius

Related Information:

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