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Letters to the Editor |
Biomed. Mass Spectrom. Unit, Univ. of New South Wales, Sydney, NSW, Australia 2052
a Author for correspondence.
To the Editor:
Taran et al. (1) recently stated that "immunoassays of catecholamine remain the preferred method for routine measurement of these molecules in biological fluids." A perusal of the relevant literature for pheochromocytoma or neuroblastoma diagnosis over the past 20 years will show this to be a dubious assertion. Rather, HPLC with electrochemical detection (HPLC-ED) appears to be in routine use by >90% of teaching hospital and major clinical laboratories worldwide. Although the 1991 review (2) cited by these authors to support their statement does refer to the putative use of immunoassay in the measurement of catecholamine metabolites, it is concluded that initial attempts in this direction suffer from marginal sensitivity and specificity (2). More recent reviews on the diagnosis of pheochromocytoma make no mention of immunoassay as an analytical method in this area (3)(4).
The authors are clearly expert in the development of immunoassays for a wide range of clinically important analytes, but we do not believe some of the generalizations made in their paper were justified; it would have been preferable, moreover, if they had (e.g.) indicated the limitations of their methodology when applied to pheochromocytoma diagnosis. Additionally, most of the literature they cite is pre-1990 and does not reflect newer concepts in the diagnosis of catecholamine-producing tumors. The propitious production of a single monoclonal antibody to homovanillic acid (HVA) (1) with suitable specificity might be applicable in routine use as part of a screening procedure for neuroblastoma, but perhaps the authors should also have noted that testing for increased HVA alone is insufficient for biochemical diagnosis of all neuroblastomas (5).
References
CEA, Serv. de Pharmacol. et d'Immunol., DRM, CEA-Saclay, 91191 Gif sur Yvette, France
a Author for correspondence.
To the Editor:
The article of Taran et al. (1) sought to demonstrate that a direct immunological assay of HVA in urine could be developed by using a monoclonal antibody specially selected for this purpose. We have shown that the resulting assay for specific detection of this urinary metabolite correlates well with measurements made by HPLC-ED, which is unquestionably the most widely used method for assay of catecholamine metabolites.
In our view, the type of assay we have developed represents an important advance because immunological assays are clearly more suited than chromatographic methods to routine measurement of large numbers of samples. Furthermore, nonisotopic immunoassays are now commonly used by clinical biology laboratories lacking access to techniques like HPLC-ED. Development of assays like ours therefore provides readily accessible techniques for accurate measurement of substances that are indirect markers of certain tumors. The development of such immunoassays is limited by the obtaining of antibodies that are "genuinely" specific to each of the catecholamine metabolites—not easy for this category of low-Mr haptens. It is, however, possible, and our work proves this, as does a recent study published in Clinical Chemistry [2]. Even if their development demands a great deal of work, we are convinced that immunological assays of specificity fully matching that of chromatographic methods will in time become widely available.
Our intention was not to downplay the merits of chromatographic methods, which are indeed well suited to the measurement of this type of molecule. If Smythe and Duncan have interpreted our article in this manner, it may well be that we were rather overenthusiastic in stating our case. We have no desire whatever to spark off a potential war of words between immunologists and those who champion chromatographic techniques in this field.
Last, we agree with the idea that the measurement of HVA alone is not sufficient to establish a biochemical diagnosis of all neuroblastomas, and this is not written in our paper.
References
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