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Thyroglobuline (Tg) is a large molecule of high molecular weight mainly indicated in monitoring differentiated thyroid cancer (DTC), its measurement remains difficult. We report the case of a patient who underwent total thyroidectomy for a poorly differentiated thyroid insular carcinoma. Despite several (131)I treatments, a progressive elevation of serum Tg is observed. A control performed in another laboratory using an immunoradiometric assay (IRMA Cisbio) returns an undetectable value (< 0,2 mg/L). A new sample was simultaneously sent to different laboratories. Three nonisotopic immunometric assays showed high values of Tg while the IRMA assay, considered the gold standard, gave a result below the detection threshold. The absence of Tg antibodies and of anti-mouse antibodies was confirmed. The IRMA Kit manufacturer agreed to carry out an expertise. After changing their detection antibody, the presence of a high Tg was demonstrated, in agreement with non-isotopic techniques. The expertise conclusion was a lack of detection by the IRMA Tg assay. This incident was notified to AFSSAPS by the manufacturer.

A permanent and quantitatively abnormal proteinuria (> 150 mg/ 24 h) found at the laboratory should be followed by an identification and quantification of all proteins present. Specific immunochemistry techniques (immunoturbidimetric or immuno-nephelometric) are almost exclusively used for measuring albumin (or microalbuminuria) in nephropathic diabetic patients. Measurement of monoclonal free light chains is not recommended due to poor accuracy. Determination of other small proteins (molecular mass, MM < 40 kDa), transferrine, immunoglobulins G (assessment of selectivity) is far less frequent and Tamm-Horsfall protein is measured in specialized laboratories. Global electrophoresis techniques are the reference methods for the study of urinary proteins. Significant progress have been made during the past ten years in terms of sensitivity (analysis down to 50 mg/L total protein with no need to concentrate urinary specimens) and separation (high resolution or according to MM). Improvement in sensitivity is a key point for the diagnostic and follow-up of low grade or treated gammapathies. Electrophoretic separation according to MM is perfectly adapted to visual typing of renal proteinuria (glomerular, tubular or mixed) and overload proteinuria, particularly by monoclonal free light chains (MM: 25 kDa, Bence Jones proteinuria) allowing their quantification by densitometry. Immunofixation combining electrophoresis and immunoprecipitation in gel has emerged as the reference technique to identify monoclonal proteins. Data obtained by urinary protein analysis need to be compared with serum results for interpretation.

Total protein analysis is one of the most frequent laboratory analyses in urine. A proteinuria above 150 mg/L is often observed in a random way in preventive or school medicine (dipsticks) or during laboratory analysis (quantitative determination). Complete (quantitative, then qualitative) and repeated evaluation of proteinuria is of major interest for the clinician to establish a diagnosis of abnormality and for therapeutic follow-up of a nephropathy, uropathy or a non-renal disease (diabetes, multiple myeloma). Most frequent (90% of cases) and severe forms of proteinuria are of glomerular type, associated to the nephrotic syndrome, hypertension, and progressive renal failure. Attention should be paid by the biologist to the pre-analytical phase (specimen collection, treatment, and storage), to clinical data, and to prescription of drugs that could interfere with protein analysis. During the last past 10 years, significant analytical advances have been made: dipstick analysis has been dropped (false positives and most importantly false negatives) as manual precipitation techniques with turbidimetric detection (poor inter-laboratory coefficients of variation, CV), replacement of Coomassie blue by pyrogallol red (improved practicability). Urinary quality control data reflect these positive changes, as demonstrated by a dramatic reduction in reported CVs. There is, however, still no reference method for total urinary protein determination and limits of existing pyrogallol red methods should be emphasized: variable reagent composition between manufacturers (such as the presence of SDS additive), limited sensitivity, difficulty in the choice of a calibration material, underestimation of free light chains, and interference with gelatin based vascular replacement fluids.

Melanoma is the most agressive skin cancer in humans. The most important prognostic factors are the histological features of the tumor, while the clinical ones play a secondary role. Melanoma progression is characterized by the metastatic process which directly threatens the patients life. Unfortunately, routine imaging methods cannot estimate early enough this metastatic risk. Are biologic markers of cancer progression more efficient than those applied in everyday practice? Are they able to evaluate the metastatic risk and thus help the therapeutic strategy? In this review, we analysed the analytical and the clinical aspects of biologic markers of cutaneous melanoma currently available or in development. At the present time it is very difficult to distinguish one single marker of melanoma progression in the blood which correlates with the stage and the prognosis of melanoma. The most specific and sensitive enough are the melanoma associated antigens protein S-100, MIA (melanoma inhibiting activity) and the melanin precursors 5-S-cysteinyldopa and the ratio L-dopa/L-tyrosine. Tyrosinase mRNA remains the best target for the detection of circulating metastatic melanoma cells by RT-PCR. Simultaneous detection of several markers might be useful if they are carefully selected. Despite the progress in the field, more clinical studies should be performed for the development of new techniques or improvements of the existing ones for the follow-up of cutaneous melanoma.