PCA3 is a new molecular biology test performed on urine samples.

PCA3 (Prostate Cancer Gene 3), formerly known as DD3, is a gene first identified in 1999 that synthesises no known proteins but is expressed in the form of messenger RNA specific to cancerous prostate cells.
The PCA3 gene is overexpressed in cancerous prostate cells compared with normal prostate tissue and benign hypertrophic tissue, whereas PSA expression is similar in both benign and malignant prostate cells. This test allows determination of expression of messenger RNA of PCA3 gene and calculation of a specific value:
score = [mRNAPCA3/mRNAPSA]x1000
Concomitant assay of mRNA and PSA allows validation of sample quality with standardisation of results.

Why should a PCA3 test be requested?

Although PSA is today an essential marker, it is far from perfect in terms of sensitivity and specificity, which can result in the performance of unnecessary prostate biopsies.
What may be concluded from a negative initial biopsy?
· either the biopsy has missed the tumour
· or there is no cancer.

Depending on the context, an answer may be provided by further biopsy. In 25% of patients, cancer is in fact diagnosed at the second biopsy.

It is here that PCA3 is extremely valuable:
· score of < 35: low probability of detection of prostate cancer,
· score of > 35: high probability of detection of prostate cancer and thus indication for further biopsy

Performance in terms of PCA3 score is independent of total serum PSA.
The PCA3 score is independent of prostate size. It is correlated with the prostatectomy Gleason score.

The PCA3 score in itself is insufficient for diagnosis; it simply allows risk evaluation, like PSA, but with greater specificity. This analysis is performed in addition to PSA on account of the associated pre-analytical constraints, its costs and the technical requirements.

There are several types of peripheral neuropathy of autoimmune origin, including sensitive neuropathy associated with monoclonal IgM, associated with the presence of antibodies directed against the myelin structures, including anti-MAG Ab and neuropathy associated with antibodies directed against membrane glycolipids, known as gangliosides, the target of many auto-antibodies.

Anti-GM1 IgM-class antibodies are detected in 80 % of chronic multifocal motor neuropathy with conduction blocks. These antibodies can cross-react with GD1b.

Anti-GM1 IgG-class antibodies are prescribed in pure motor or sensitive-motor forms of Guillain Barré syndrome (or acute axonal polyneuropathy). They often occur after a viral or bacterial infection of the respiratory or digestive tract (Campylobacter jejuni). These antibodies are also present in chronic motor neuropathy.

Pheochromocytomas (PH) are tumours of the adrenal or extra-adrenal medulla (paraganglioma) and are one of the curable causes of arterial hypertension. Detecting PH is essential, as it can be fatal in cases of heart rhythm disorders and attacks of hypertension. It can also be a sign of multiple endocrine neoplasias (MEN) and can sometimes be malignant. When a diagnosis of PH is suspected due to a paroxysmal set of symptoms (palpitations, profuse sweating, pallor, headaches, etc.) or chronic symptoms in cases where the tumour is continuously secreting (variable hypertension resistant to treatment with characteristic episodes of orthostatic hypotension), biological assays must provide diagnostic evidence before any topographic exploration of lesions is undertaken. PH secretes catecholamines (epinephrine E and norepinephrin NE) in variable proportions according to their location.

Catecholamines are metabolised by a COMT (catechol-O-methyl-transferase) enzyme in the general circulation and partly in the tumour in the form of metanephrines, a generic term describing metanephrine derived from epinephrine (E) and normetanephrin derived from norepinephrin (NE). Plasma assays of E and NE catecholamines are not very useful for diagnosis due to the short biological half-life of these two amines in the circulation. Moreover, the positive biological diagnosis of PH has long been based on the assay of free catecholamines and metanephrines in 24-hour urine samples sometimes collected over two or 3 successive days to increase the chances of diagnosis.

Technological progress over the past number of years now enables the assay of plasma free metanephrines with the help of a liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS). Due to their long biological half-life, plasma free metanephrines are lasting markers of PH hypersecretion. Their assay represents a step forward because although their diagnostic sensitivity appears to be equivalent to that of urinary metanephrines, the practicability of sample-taking (a blood sample that can be taken at any time) is an important advantage compared to the complicated 24-hour urine collections.

N.B.: This test is connected with diagnosing an individual's genetic characteristics (molecular genetics) and as such is subject to specific regulations. Always enclose the test order form for genetic characteristics as well as a genetic characteristics consent form. These documents are available on our website: www.pasteur-cerba.com
->Testing information/Test requisition Form.

Since the beginning of November 2007, we have been carrying out analysis on IgG-class serum autoantibodies, associated with idiopathic inflammatory myositis, mainly polymyositis (PM) and dermatomyositis (DM).

These antibodies are the following:

The antisynthetase antibodies, antibodies directed against the aminoacyl-tRNA synthetases, enzymes allowing one of the 20 amino acids to be fixed on its transfer RNA in the cell cytoplasm. They give a cytoplasmic fluorescence on HEp-2 cells that is not constant, which is why it is preferable to characterise them individually.
These antibodies define the antisynthetase syndrome, which associates myositis with an elevation of muscular enzymes, pulmonary fibrosis, polyarthritis, Raynaud’s phenomenon and “mechanic’s hands”.
In 60 to 80% of the antisynthetase syndromes, the antibody directed against histidyl-tRNA synthetase, also called anti-Jo1 or anti-PL1, is found. This antibody is usually sought among the soluble nuclear anti-antigenic antibodies or ECT.
In 10 to 15% of cases, anti-PL7, an antibody directed against threonyl-tRNA synthetase is detected, and in 5 to 10% of cases, anti-PL12, an antibody directed against alanyl-tRNA synthetase.
In spite of their low sensitivity (they are only found in 20 to 30% of myositis cases), these antibodies are very specific (>95%).
Other antisynthetase antibodies have been reported (anti-EJ, OJ, JS, KS), but cannot routinely be identified at the present time.

Anti-SRPs (Signal Recognition Particle) are rarer (5% of PM-type myositis). Unlike in the antisynthetase syndrome, the clinical presentation does not display cutaneous or articular symptoms or interstitial lung disease, but has signs of severe myositis, often with myocardial involvement. These antibodies produce a cytoplasmic fluorescence close to that of the antisynthetases and antiribosomes.

Anti-Mi-2 antibodies are very specific to DM, and can be accompanied by interstitial lung disease. On HEp-2 cells, these antibodies mark the nucleus with a finely granular fluorescence of almost homogeneous appearance.

Anti-PMScl antibodies are observed in polymyositis-scleroderma overlap syndromes.
The condition can begin in the form of a dermatomyositis complicated by systemic scleroderma, or the opposite can happen, starting with a scleroderma associated with myositis. These antibodies mark the nucleoli of HEp-2 cells with a homogeneous fluorescence.

Anti-Ku antibodies have been described in overlap sclerodermatomyositis-type syndromes, especially in the Japanese population, but they are also observed in Gougerot-Sjögren, lupus and scleroderma without myositis. Similar to
anti-PMScl antibodies, the anti-Ku antibodies mark the nucleoli of HEp-2 cells.