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A team led by researchers at the Johns Hopkins Kimmel Cancer Center reports that a new lab test developed to identify chemical changes in a group of cancer-related genes can accurately detect cancerous or benign bad tumors and to do it in much less time than standard gold -tests on biopsied bad tissue.
Although the results are preliminary and require further validation from larger groups of people, the researchers indicated that the test could potentially significantly reduce the time (minimum of one month, up to 15 months) generally required to ask a definitive diagnosis of bad cancer among the poorest. countries. A rapid diagnosis has already been proven: it improves survival for all cancers by reducing waiting times for surgical and other treatments. A report on the test, which exploits the tendency of certain cancer-related genes to undergo attachment to a chemical group, according to a process known as methylation, is published online in the July issue of Clinical research on cancer.
"The diagnosis is a huge bottleneck to start a treatment, especially in developing countries that have a small number of pathologists available to examine bad cancer biopsies and who serve a large population "said Saraswati Sukumar, Ph.D., responsible for the study, professor of oncology and pathology. at the Johns Hopkins Kimmel Cancer Center. "This means that a test like ours could be particularly useful in countries with fewer resources and where bad cancer mortality rates are much higher than in developed countries."
Breast cancer cases are increasing worldwide, notes Sukumar. Globally, the incidence of bad cancer is increasing steadily. In 1980, GLOBOCAN reported 641,000 new cases of bad cancer worldwide. By 2018, the estimated incidence of bad cancer worldwide was 2.1 million cases (an annual increase rate of 3.2%) and 626,000 deaths from this cancer.
In developing countries, women present with advanced bad lesions due to the lack of bad cancer screening programs / pathology. Even after biopsy palpable mbades, the diagnosis is delayed because most countries in sub-Saharan Africa have on average less than one pathologist per million inhabitants. Pathology and treatment services are only available in regional hospitals. This, combined with limited access to effective treatments, leads to high case fatality rates. For the few extremely overloaded pathologists, an accurate, fast and resource-efficient test that can be used in screening clinics to detect malignancies would greatly help prioritize patients requiring accelerated pathological and clinical badessment, while reducing the burden. overloaded health systems, Sukumar explains
The higher mortality rates in developing countries are the result of social prejudices that prevent many women from seeking prompt treatment and lack of health care resources. However, the time between biopsies of diagnosis, which can be up to 15 months in less well-equipped regions than a few days or weeks in the United States, is an important factor.
Given the current challenges in pathology services in most low- and middle-income countries, the time to process pathology results is several weeks and often several months in some countries. A retrospective review of the timeframe of the Butaro Cancer Center in Rwanda revealed that it took an average of 32 days from receipt of the specimen to notification. Another study reported delays of 15 months after biopsy. A retrospective badysis conducted in Malawi, a country in South-East Africa, identified an average of 43 days for out-of-pocket cancer samples and 101 days for unpaid, fund-based samples. public. A Mexican study reported delays of six to 10 months for a pathology diagnosis.
Seeking to shorten the time between biopsy and diagnosis, Sukumar and colleagues at the Johns Hopkins Kimmel Cancer Center, Pathology, Surgery and Radiology Departments at Johns Hopkins University School of Medicine and the School of Health Johns Hopkins Bloomberg and Cepheid employees developed a new technology platform. Here, a patient's biopsy sample is loaded into cartridges and inserted into a machine that tests the levels of gene methylation – a chemical addition to genes that results in changes in the activity of the cells. Genoa. This platform returns the results of the methylation marker within five hours.
To develop the test, the researchers collected 226 samples of bad tissue. These samples came from women in the United States, China and South Africa. Their ages ranged from 25 to 85 years and represented all subtypes of bad cancer: positive estrogen receptors, HER2 positive, triple negative bad cancer, ductal and lobular cancers, and ductal carcinoma in situ (DCIS). Four different types of benign lesions and normal bads were also sampled. A genetically diversified collection ensured that the results would be widely applicable. The sampling of malignant and benign lesions allowed the researchers to distinguish the differences in methylation between the two groups.
Using these samples, Sukumar and colleagues Bradley Downs, Ph.D., and Mary Jo Fackler, Ph.D., badessed the usefulness of 25 genes that previous studies often had-well. that not always – was methylated differently in bad cancer. and benign lesions. Eventually, they restricted their candidate genes to a panel of 10 with methylation characteristics that were more likely to distinguish between a majority of malignant and benign learning samples.
The researchers evaluated this panel of 10 genes using 246 additional bad tissue samples, showing similar success in the panel's ability to distinguish cancer from non-cancer.
They then conducted a pilot study of 73 samples from Portugal and Hong Kong of fine-needle aspirations obtained from bad lesions deemed suspicious by mammography. The test differentiated the 49 benign lesions from the 24 cancerous lesions with an accuracy of 96%.
These results suggest that the test looks promising as a "first pbad" for distinguishing malignant tumors from benign tumors and tumors, says Sukumar. With a 5-hour return on performance, lower skills required to run the test, and relatively low expenses, this could give hope of speeding up the diagnosis for thousands of women around the world.
Sukumar warns that the team's molecular test can not replace the badyzes of a pathologist, whose skills will be required to review the fundamental biopsies of the bad lesion so To obtain a definitive diagnosis and optimal therapeutic recommendations.
"We hope that if new studies confirm its value, it could push women whose methylation screening is positive in the foreground so that their biopsies can be examined quickly by the few pathologists in developing countries. "said Sukumar. "Instead of languishing for months while waiting for the diagnosis, patients can begin life-saving treatments immediately."
Other Johns Hopkins researchers involved in this study include Claudia Mercado-Rodriguez, Leslie M. Cope, Danielle Meir-Levi, Rupali Sood, Juanjuan Li, Antonio C. Wolff and Kala Visvanathan.
This work was funded by grants to the Under Armor SS (80040851), the AVON Foundation for Research (01-2017-007), Cepheid (research agreement, 90066820) and the Foundation Grant of CCSG (P30-CA006973). BD is supported by a DOD-award postdoctoral fellowship: BC171982. FS benefits in part from the NORTE-01-0145-FEDER-000003 project, Northern Portugal Regional Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund. (ERDF).
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