Specificity of Elevated Plasma EM66 Levels in Pheochromocytoma
Condition: Pheochromocytoma; Paraganglioma; Essential Hypertension
MeSH terms: Pheochromocytoma; Paraganglioma; Hypertension; Essential Hypertension
Study type: Observational

Summary: 
      Pheochromocytoma or paraganglioma are tumors generating hypertension as a symptom. Different
      biological tests are currently available to diagnose these tumors. However, they all lack
      specificity since they do not distinguish cases of hypertension without pheochromocytoma or
      paraganglioma. To improve the diagnostic specificity of these tumors, the investigators are
      testing a new marker called EM66.
    

Detailed description: 
      Neuroendocrine tumors (NT) correspond to neoplasms that develop from endocrine and
      neuroendocrine cells scattered throughout the body. They are characterized by the occurrence,
      in their cytoplasm, of dense-core secretory vesicles containing hormones, neuropeptides and
      acidic proteins such as granins. The diversity of NT (from hypophysis, pancreas, adrenal,
      gastrointestinal tract) makes very difficult the identification and evaluation of the
      different types of tumors by the diagnostic and prognostic tools currently available. We have
      thus established a research program aimed at identifying new biological markers for the
      detection, the prognosis and the follow-up of NT by seeking in tumor and plasma samples of
      patients, granin-derived peptides. Our program was initiated on one type of NT :
      pheochromocytoma. These neoplasms correspond to tumoral chromaffin cells mainly originating
      from the adrenal medulla. It is considered that 10 % of pheochromocytoma patients will
      develop metastases and, currently, except in the presence of metastases, there are no means
      to predict malignancy of the tumor. We setup a radioimmunoassay of EM66 (a secretogranin
      II-derived peptide) that allowed us to demonstrate that (i) plasma concentrations of the
      peptide are significantly elevated in pheochromocytoma patients, (ii) combined with other
      biological tests EM66 measurement increase the diagnostic sensitivity for these neoplasms,
      (iii) after surgical removal of the tumor, plasma EM66 concentrations rapidly return to basal
      level and, (iv) intra-tumoral EM66 concentrations are higher in benign than in malignant
      pheochromocytomas (Yon et al., 2003, Guillemot et al., 2006). These results reveal that EM66
      constitutes a novel tool for the diagnosis, prognosis and follow-up of pheochromocytoma. In
      the frame of a clinical use of an EM66 measurement test, it is necessary to evaluate the
      specificity of this marker. For instance, renal deficiency, hypergastrinemia, reduction of
      renal clearance, type A gastritis, Crohns disease, or proton-pump inhibitory treatment, lead
      to increase plasma chromogranin A (CgA) concentrations (false-positive cases). In addition,
      while hypertension account for one of the symptoms of pheochromocytoma patients, in essential
      hypertensive patients, CgA levels are higher than in normotensive individuals. The main
      objective of our clinical transfer research project consists to study the specificity of the
      measurement of EM66 as a diagnostic and prognostic marker of pheochromocytoma. This
      multicentric study will allow us to compare plasma EM66 levels in pheochromocytoma patients
      with a cohort of essential hypertensive patients. At the same time, in a long-range prospect,
      due to the lack of malignancy markers for these tumors, we will investigate if plasma or
      tumor EM66 levels are correlated to the differentiation status of pheochromocytomas, and if
      the expression level of a set of genes that we identified by a transcriptomic approach
      developed in the laboratory, is associated with the malignant status of the tumors. The
      stakes of this transfer research, involving our laboratory and the Center for Clinical
      Investigations (CIC) of Rouen and Lille, are to provide an easy and simple novel tool to
      practitioners and anatomo-pathologists for the screening, the evaluation and the follow-up of
      patients with neuroendocrine tumors.
    

Intervention name(s): plasma EM66 & CgA levels assessment; usual follow up with regular EM66 & Cga levels assessment
Intervention type(s): Other; Other
Intervention description(s): After inclusion checking to eliminate the presence of pheochromocytoma / paraganglioma, a blood sample will be drawn to assess plasma EM66 and CgA levels.; Patients with pheochromocytoma / paraganglioma will be followed-up as the international standards recommend.
Regularly, blood samples will be drawn for the usual assessment of CgA levels and also EM66 (research purpose) levels.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        two distint population will be involved :

          -  patients with pheochromocytoma or paraganglioma

          -  patients with essential hypertension
      
Biospecimen description: 
      5 ml blood sample on EDTA to collect 2,5 ml plasma, kept at -80°C, once a year.
    
Keywords: pheochromocytoma; paraganglioma; hypertension