Researchers identify new prostate cancer marker detectable in urine

A clump of prostate cancer cellsResearchers in the US have found a new marker of the aggressiveness of prostate cancer that is detectable in the urine of men with the malignancy.  Sreekumar et al. discovered that levels of sarcosine, a common amino acid found in many biological tissues, are higher in invasive prostate cancers than in benign cancers and are detectable in the urine of affected men.

Currently, prostate cancer is detected by measuring blood levels of a marker called prostate specific antigen (PSA). The diagnosis is then confirmed by taking a tissue sample (biopsy) from the prostate using a fine needle – an uncomfortable and undignified process – and examining it under a microscope.

If further trials confirm that sarcosine levels in the urine do reflect how advanced a prostate cancer is, measurement of this marker could be used as a noninvasive way to predict the aggressiveness of a cancer and thus a patient’s prognosis.

In this study, the authors recorded all the metabolites (low molecular weight molecules produced by cells) found in samples from patients with various stages of prostate cancer, ranging from benign cancer to advanced metastatic cancer.  In total, 1,126 metabolites in 262 clinical samples related to prostate cancer were profiled.  The authors then compared the metabolites found in the various types of tumor tissues in order to unearth ‘molecular signatures’ that distinguished the different stages of prostate cancer.

In total, 87 metabolites that distinguished prostate cancer from benign prostate tissue were found, and the levels of six of these metabolites were even higher in metastatic cancer than in any other stage of disease.  Sarcosine, an N-methyl derivative of the amino acid glycine, was highly increased in metastatic samples and, importantly, was undetectable in the benign samples.

The authors then tested out what happened when they eliminated the enzyme glycine-N-methyl transferase, which is crucial for the production of sarcosine from its precursor glycine.  The invasive properties of prostate cancer cells in culture were attenuated when this enzyme, and thus sarcosine, was absent. Addition of sarcosine to benign prostate epithelial cells or knockdown of the enzyme that is responsible for sarcosine degradation caused noncancerous cells to become invasive. Taken together, these findings suggest that not only is sarcosine a marker of cancer aggressiveness, it also has a role in endowing a cancer with malignant properties.  Components of the sarcosine pathway may thus serve as new targets in the development of drugs that combat prostate cancer metastasis.

Lastly, the authors measured levels of sarcosine in urine specimens from individuals who had been definitively diagnosed with prostate cancer on the basis of PSA levels and prostate biopsy and compared these results with those from individuals who were biopsy negative.  Levels of sarcosine were significantly higher in the urine of men with prostate cancer than in those without, confirming that measurement of sarcosine in the urine may act as an indicator of prostate cancer.

Senior study author Dr Arul Chinnaiyan told The Independent: “One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up over treating our patients because physicians don’t know which tumours will be slow-growing. With this research, we have identified a potential marker for the aggressive tumours.”

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Sreekumar A et al. (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Nature 457 (7231): 910-914 DOI: 10.1038/nature07762

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Skin test to detect Parkinson’s disease

A recent study published in the Journal of Neuropathology & Experimental Neurology has shown that neural signs of Parkinson’s disease can be identified by taking a simple skin sample.

Parkinson’s disease is a progressive neurodegenerative disease that affects about 1 in every 500 people in the UK. There is no biochemical test to definitively diagnose Parkinson’s disease; diagnoses are instead made on the basis of various clinical assessments. Parkinson’s disease is, however, characterized by the presence of Lewy bodies (LBs) – tiny protein deposits in nervous tissue.

LBs can only be identified from a tissue sample, which is then stained and examined under a microscope (see right). These proteins tend to accumulate in the central nervous system and in the sympathetic ganglia, nervous tissue that runs like train tracks down either side of the spine – places that are nearly impossible to get biopsy samples.

In this study, the authors looked for LBs in various tissues in 279 patients undergoing autopsy. A total of 85 patients had evidence of LBs in their central nervous system, so were diagnosed as having had a LB disease (LBD) – Parkinson’s with or without dementia, dementia with LBs or LB-related progressive autonomic failure.

The authors then examined skin biopsy samples taken the patients with proven LBD and found that 20 (23.5%) patients showed LB pathology in the cutaneous nerves of skin samples. None of the 194 individuals who did not have LBD showed evidence of LBs in skin samples; therefore, the skin test didn’t mistakenly identify any patients as having LBD.

More specifically, LBs were found in the skin of 70% of patients who had Parkinson’s disease with dementia and in 40.4% of those who had dementia with LBs. On the other hand, LB pathology was found in the skin of only 20% of patients who had subclinical LBD, i.e. patients who would have had few symptoms of LBD but not enough signs to meet all the criteria for a diagnosis. This skin biopsy test might not, therefore, be a useful test for early diagnosis in individuals suspected of having LBD.

When the authors looked at the clinical records of the patients that they had autopsied, they found that LBD patients who had evidence of LB pathology in their skin were more likely to have been bedridden and unable to walk independently before they died than were those patients with LBD who did not have cutaneous LB pathology (P<0.001 style="font-style: italic;">P=0.065, respectively). This finding suggests that skin biopsy testing could be used to predict which patients’ physical functioning might be affected most seriously by their disease, and physiotherapy could be prescribed accordingly.

Ikemura et al.’s study is the first to find evidence of LB pathology in the skin of patients with LBD; however, their results do not support the use of skin biopsy as an early diagnostic test. Testing for LBs in the skin could be used to confirm the diagnosis in a patient with clinical Parkinson’s disease or dementia with LBs and to predict the effect the disease might have on their physical functioning, both of which could help clinicians tailor treatment.

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Ikemura M, Saito Y, Sengoku R, Sakiyama Y, Hatsuta H, Kanemaru K, Sawabe M, Arai T, Ito G, Iwatsubo T, Fukayama M, Murayama S (2008). Lewy Body Pathology Involves Cutaneous Nerves. J Neuropathol Exp Neurol, 67 (10), 945-953 PMID: 18800013

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Do common pain medications mask signs of prostate cancer?

A study recently published in the journal Cancer has suggested that common painkillers such as paracetamol and aspirin might affect blood levels of a marker commonly used to diagnose prostate cancer.

In this study, Singer et al. examined levels of prostate specific antigen (PSA) in the bloodstream of 1,319 men aged over 40 years. PSA is a protein produced in the prostate gland. Blood levels of PSA will be minuscule in healthy men, but raised levels often indicate the presence of prostate cancer. If a simple blood test detects serum levels of PSA higher than a specific threshold (4 ng/ml to be exact), your doctor will be booking you in for a digital rectal examination with a prostate cancer specialist faster than you can say “He wants to stick his finger where?!”

In addition, study participants were asked how often they took analgesic drugs classed as non-steroidal anti-inflammatory drugs (NSAIDs) – common types being aspirin and ibuprofen – or the drug acetaminophen, which you’ll probably be familiar with as paracetamol. NSAIDs and acetaminophen act as painkillers by reducing inflammation. Given that inflammation in the prostate has been implicated in the development of prostate cancer, the authors of this study wanted to find out whether NSAIDs or acetaminophen affected the risk of prostate cancer in men who took these drugs.

The results of this study showed that serum levels of PSA in men who took NSAIDs or acetaminophen “nearly every day” were considerably lower than levels in men who did not take either drug. Seeing as this study didn’t then follow these men for several years to find out whether there were fewer instances of prostate cancer in the men who took these analgesics than in those who didn’t, it is not clear whether this decrease in PSA levels means that the drugs reduce the risk of cancer. In fact, it it possible that NSAIDs and acetaminophen may reduce serum levels of PSA despite suspicious goings on in the prostate and thus cause doctors to miss cases of prostate cancer, which would otherwise be flagged by raised PSA levels.

So what are the implications of the study? Should men chew down aspirin every day to prevent prostate cancer, or would they make detection of the malignancy more difficult for their doctor by doing so? Dr Eric Singer, one of the authors of this study, told Reuters news, “If you’re a guy who’s close to the upper limit of normal [in PSA levels] or would have been over the upper limit and now you’re under it because of [these drugs], that could certainly change whether or not you would be referred for a biopsy [to check for a tumor]”. He also emphasizes that these findings are preliminary and shouldn’t prompt men to change their behaviour.

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Eric A. Singer, Ganesh S. Palapattu, Edwin van Wijngaarden (2008). Prostate-specific antigen levels in relation to consumption of nonsteroidal anti-inflammatory drugs and acetaminophen Cancer DOI: 10.1002/cncr.23806

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