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PCA3

From Wikipedia, the free encyclopedia

Prostate cancer antigen 3 (PCA3, also referred to as DD3) is a gene that expresses a non-coding RNA. DD3 expression was found in kidney and prostate tissue, however in kidney tissue, it was found at insignificant levels. DD3 has significant expression and specificity in detecting prostate malignancies and therefore can be utilized as a tissue biomarker for prostate cancer detection.

Contents

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• 1Use as biomarker
• 2Discovery
• 3References
• 4Further reading
• 5External links

Use as biomarker[edit | edit source]

The most frequently used biomarker for prostate cancer today is the serum level of prostate-specific antigen (PSA), or derived measurements of it. Prior to PCA3 a digital rectal examination (DRE), PSA level tests, prostate volume measurement and patient history were used to gauge if a patient will undergo a prostate biopsy. However, since PSA is prostate-specific but not cancer-specific, it is an imperfect biomarker. For example, PSA levels can increase in older men with benign prostatic hyperplasia and prostatitis. Several new biomarkers are being investigated to improve the diagnosis of prostate cancer. Some of these can be measured in urine samples, and it is possible that a combination of several urinary biomarkers will replace PSA in the future.^[5]

With the increase of prostate cancer present in North America, there is a higher demand for prostate biopsies leading to approximately 1 million biopsies performed each year. The PCA3 test can prevent unnecessary biopsies since it's score is independent of prostate volume. In order to facilitate patient counseling, risk calculators such as nomograms, or prediction scales are used. The PCA3 score has a cut-off margin of 35, resulting in a 2-2.5 fold increased likelihood that men would have prostate cancer when the score is higher than 35. This diagnostic tool can give insight regarding the next steps for men who have previously had a negative biopsy, have elevated PSA levels, or men with a suspicious DRE but a low PSA level. The results of the PCA3 test help to differentiate the potential aggressiveness, or presence of prostate cancer, helping clinicians to decisions for treatment, and further diagnostic options unlike with PSA results. For example, the results can indicate men will have a higher probability of an aggressive form of cancer, or prostate cancer depending on their score, factoring in false positive and negative predictive value. Different outcomes of the extensive prostate cancer screening will determine whether the patient needs chemotherapy, such as androgen deprivation therapy, radiation therapy, surgery to remove the prostate (prostatectomy), or if the patient will remain under watchful waiting.. PCA3 has shown to be useful in predicting the presence of malignancy in men undergoing a repeat  prostate biopsy.^[8][9] This means that it could be useful clinically for a patient for whom digital rectal examination and PSA suggest possible prostate cancer, but the first prostate biopsy returns a normal result. This occurs in approximately 60% of cases, and on repeat testing, 20-40% have an abnormal biopsy result.^[10]

This method of testing also aids in handling patients who have a high cancer risk, or who would like to exhaust every test, or non-invasive option before determining if a biopsy is needed. The The PCA3 scoring spectrum ranges from 4 to 125. A higher score represents an increased probability of a positive biopsy, whereas a lower score represents a lower probability for a positive biopsy. Compared to serum PSA, PCA3 has a lower sensitivity but a higher specificity and a better positive and negative predictive value.^[6] Other uses that are being studied for PCA3 include its correlation with adverse tumor features such as tumor volume, grading (Gleason score) or extracapsular extension. These studies have so far produced conflicting results.

The PCA3 gene is one of the original prostate cancer biomarkers that is used as a clinical diagnostic tool. The PCA3 assay has been approved by the US Food and Drug Administration and is Community European approved for men who have had a prior negative biopsy. A commercial kit called the Progensa PCA3 test is marketed by the Californian company Gen-Probe. Gen-Probe acquired rights to the PCA3 test from Diagnocure in 2003. Gen-Probe began clinical testing in 2004 and this data was presented at the American Urological Association annual meeting in 2006. Diagnocure developed the urine assay prototype, which they called uPM3, and later formed the name PCA3. Royalties of 16% of cumulative sales of PCA3 kit are paid to Diagnocure. Diagnocure is quoted on TSX as CUR.TO (Canada) ^[10] [14]

Discovery[edit | edit source]

PCA3 was discovered by Dr. Marion Bussemakers in 1993 in William B. Issacs laboratory at the Brady Urological Institute of John Hopkins University. Further research was performed in laboratories supervised by Dr. Bussemakers in the Netherlands, and the first clinical application of PCA3 was conducted at the University Hospital in Nijmegen. The DD3 gene is located on chromosome 9 and more specifically 9q21-22. The prostate cancer cell line LNCaP has a high androgen sensitivity and is the only cell line to express DD3, therefore there is a high expression of PCA3.