Urinalysis Lab Grade 12

[Rita Seliba]

Thetest, called MyProstateScore2.0, or MPS2, looks at 18 different genes linked to high-grade prostate cancer. In multiple tests using urine and tissue samples from men with prostate cancer, it successfully identified cancers classified as Gleason 3+4=7 or Grade Group 2 (GG2), or higher. These cancers are more likely to grow and spread compared to Gleason 6 or Grade Group 1 prostate cancers, which are unlikely to spread or cause other impact. More than one-third of prostate cancer diagnoses are this low-grade form. Gleason and Grade Group are both used to classify how aggressive prostate cancer is.

"Our standard test is lacking in terms of its ability to clearly pick out those who have significant cancer. Twenty years ago, we were looking for any kind of cancer. Now we realize that slow-growing cancer doesn't need to be treated. All of a sudden, the game changed. We went from having to find any cancer to finding only significant cancer," said co-senior study author John T. Wei, M.D., David A. Bloom Professor of Urology at Michigan Medicine.

Prostate-specific antigen, or PSA, remains the linchpin of prostate cancer detection. MPS2 improves upon a urine-based test developed by the same U-M team nearly a decade ago, following a landmark discovery of two genes that fuse to cause prostate cancer. The original MPS test, which is used today, looked at PSA, the gene fusion TMPRSS2::ERG, and another marker called PCA3.

"There was still an unmet need with the MyProstateScore test and other commercial tests currently available. They were detecting prostate cancer, but in general they were not doing as good a job in detecting high-grade or clinically significant prostate cancer. The impetus for this new test is to address this unmet need," said co-senior author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. Chinnaiyan's lab discovered the T2::ERG gene fusion and developed the initial MPS test.

To make MyProstateScore even stronger at identifying high-grade cancers, researchers used RNA sequencing of more than 58,000 genes and narrowed it to 54 candidates uniquely overexpressed specifically in higher-grade cancers. They tested the biomarkers against urine samples collected and stored at U-M through another major study, the National Cancer Institute's Early Detection Research Network. This included about 700 patients from 2008-2020 who came for a prostate biopsy due to an elevated PSA level.

This first step narrowed the field to 18 markers that consistently correlated with higher grade disease. The test still includes the original MPS markers, plus 16 additional biomarkers to complement them.

From there, the team reached out to the larger Early Detection Research Network (EDRN), a consortium of more than 30 labs across the country that are similarly collecting samples. This ensured a diverse, national sampling. Knowing no specific details about the samples, the U-M team performed MPS2 testing on more than 800 urine samples and sent results back to collaborators at the NCI-EDRN. The NCI-EDRN team assessed MPS2 results against the patient records.

"If you're negative on this test, it's almost certain that you don't have aggressive prostate cancer," said Chinnaiyan, S. P. Hicks Endowed Professor of Pathology and professor of urology at Michigan Medicine.

Moreover, MPS2 was more effective at helping patients avoid unnecessary biopsies. While 11% of unnecessary biopsies were avoided with PSA testing alone, MPS2 testing would avoid up to 41% of unnecessary biopsies.

"In those men who have had a biopsy before and are being considered for another biopsy, MPS2 will identify half of those whose repeat biopsy would be negative. Those are practical applications for patients out there. Nobody wants to say sign me up for another biopsy. We are always looking for alternatives and this is it," Wei said.

MPS2 is currently available through LynxDx, which is University of Michigan spin-off company that has an exclusive license from the university to commercialize MPS2. Patients interested in learning more can call the Michigan Medicine Cancer AnswerLine at 800-865-1125.

Disclosures: Chinnaiyan serves on the advisory boards of Tempus, LynxDx, Ascentage Pharmaceuticals, Medsyn therapeutics, Esanik and RAAPTA therapeutics. Tomlins is an equity holder and chief medical officer of Strata Oncology. LynxDx has obtained an exclusive license from the University of Michigan to commercialize MPS2 and the TMPRSS2-ERG gene fusion. Tosoian and Chinnaiyan are equity holders and scientific advisers to LynxDx. Siddiqui, Zhang, Xiao and Niknafs have served as scientific advisers to LynxDx.

Prostate cancer is a leading cause of cancer death among men nationwide. Screening for prostate cancer typically includes a blood test to measure levels of a substance called prostate specific antigen (PSA), which is produced by the prostate gland. PSA levels can be elevated in men who have prostate cancer or certain non-cancerous conditions, like inflammation of the prostate.

Elevated PSA levels can lead to additional tests that may include a biopsy. The biopsy involves removing about a dozen small tissue samples from several areas of the prostate gland to look for cancer cells. Although biopsies are generally safe, they can be painful. They can also lead to fever, urinary tract infection, or other side effects. In many cases, the biopsy identifies slow-growing prostate cancers that would benefit from close monitoring but do not need immediate treatment.

Researchers have been searching for ways to avoid unnecessary biopsies by finding noninvasive ways to distinguish between aggressive prostate cancers that need treatment and slow-growing cancers that may never need treatment.

About a decade ago, an NIH-supported research team led by Dr. Arul M. Chinnaiyan of the University of Michigan developed a urine-based test called MyProstateScore (MPS) that is still in use. Based on two genes that are often found at high levels in the urine of men who have prostate cancer, MPS enables early detection of prostate cancer. But it does not distinguish between low-grade and more serious cancers.

In their latest study, a team led by Chinnaiyan and Dr. Jeffrey Tosoian of Vanderbilt University worked to identify a set of urine-based genes that could distinguish aggressive prostate cancers. Their findings appeared on April 18, 2024, in JAMA Oncology.

The researchers first analyzed RNA sequencing data from nearly 59,000 genes to identify a set of 54 candidate markers. All were linked to either prostate cancer overall or uniquely linked to high-grade cancers, and all were detectable in urine. Further analyses and modeling in 761 patients narrowed down the options to a combination of 17 genes that best predicted the presence of high-grade cancers. A reference gene associated with general prostate tissue was also added. The new 18-gene test was dubbed MyProstateScore 2.0 (MPS2).

MPS2 was validated by analyzing urine samples from another group of 743 men. Each received a biopsy because of elevated PSA levels. The biopsies showed that 20% of them had high-grade prostate cancer.

Validation analysis showed that MPS2 could rule out the presence of high-grade cancer with 97% accuracy. The researchers also compared MPS2 to results from other biomarker tests, including the original MPS test. The analysis showed that MPS2 was better able to identify high-grade cancers. The researchers estimated that it could help patients avoid up to 51% of unnecessary biopsies.

Urinalysis is invaluable in the diagnosis of urologic conditions such as calculi, urinary tract infection (UTI), and malignancy. It also can alert the physician to the presence of systemic disease affecting the kidneys. Although urinalysis is not recommended as a routine screening tool except in women who may be pregnant, physicians should know how to interpret urinalysis results correctly. This article reviews the correct method for performing urinalysis and the differential diagnosis for several abnormal results.

A midstream clean-catch technique usually is adequate in men and women. Although prior cleansing of the external genitalia often is recommended in women, it has no proven benefit. In fact, a recent study1 found that contamination rates were similar in specimens obtained with and without prior cleansing (32 versus 29 percent). Urine must be refrigerated if it cannot be examined promptly; delays of more than two hours between collection and examination often cause unreliable results.2

Foods, medications, metabolic products, and infection can cause abnormal urine colors (Table 1).3 Cloudy urine often is a result of precipitated phosphate crystals in alkaline urine, but pyuria also can be the cause.

The normal odor of urine is described as urinoid; this odor can be strong in concentrated specimens but does not imply infection. Diabetic ketoacidosis can cause urine to have a fruity or sweet odor, and alkaline fermentation can cause an ammoniacal odor after prolonged bladder retention. Persons with UTIs often have urine with a pungent odor. Other causes of abnormal odors include gastrointestinal-bladder fistulas (associated with a fecal smell), cystine decomposition (associated with a sulfuric smell), and medications and diet (e.g., asparagus).

Determination of urinary pH is useful in the diagnosis and management of UTIs and calculi. Alkaline urine in a patient with a UTI suggests the presence of a urea-splitting organism, which may be associated with magnesium-ammonium phosphate crystals and can form staghorn calculi. Uric acid calculi are associated with acidic urine.

Nonglomerular hematuria is secondary to tubulointerstitial, renovascular, or metabolic disorders. Like glomerular hematuria, it often is associated with significant proteinuria; however, there are no associated dysmorphic RBCs or erythrocyte casts. Further evaluation of patients with glomerular and nonglomerular hematuria should include determination of renal function and 24-hour urinary protein or spot urinary protein-creatinine ratio.

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