Biomedical subjects
Publications and source records attributed to Jean Michel Bidart.
Papillary thyroid carcinomas are characterized in 70% of cases by the presence of either a RET/PTC rearrangement, or an activating point mutation of RAS or BRAF genes that induce a constitutive activation of the MAP kinase pathway. Follicular carcinomas are characterized by the presence of a RAS mutation or of a PAX8-PPARgamma rearrangement. Inactivating mutations of the p53 gene are found only in anaplastic thyroid carcinomas.
OBJECTIVE: The diagnostic impact of chromogranin A (CgA) measurement has been studied in various neuroendocrine tumours (NET) such as pheochromocytomas, gastrinomas and neuroblastomas. Clinically nonfunctioning pituitary adenomas (NFPA) are generally diagnosed on tumoural symptoms or hypopituitarism and, except for gonadotrophins and their free subunits which may be increased in the case of gonadotrophinomas, markers of endocrine secretory activity are lacking not only for diagnostic purpose but also in the postoperative follow-up of these patients. As the presence of CgA has been demonstrated by immunohistochemistry in pituitary adenomas, we performed this study to further assess the sensitivity of CgA measurement in sporadic pituitary adenomas using a new, specific, sandwich immunoassay. SUBJECTS: We first completed a basal normative data set obtained using this assay by studying four healthy men (49 +/- 13 years old), five healthy premenopausal women (35.8 +/- 7.5 years old) and five healthy postmenopausal women (49.1 +/- 4.6 years old) basally and after TRH administration. Twenty-seven patients [12 men (64.2 +/- 11.8 years), even premenopausal women (38.4 +/- 5.7 years) and eight postmenopausal women (67.7 +/- 10.3 years)] with NFPA, 15 acromegalic patients [nine men (45 +/- 13.3 years), six women (52 +/- 14.9 years)] and 19 patients with a prolactin-secreting adenoma [four men (41.2 +/- 18 years) and 15 women (31.2 +/- 7.5 years), with a macroadenoma (n = 11) or a microadenoma (n = 8)] had basal and TRH-stimulated measurement of CgA. A gonadotrophin-releasing hormone (GnRH)-stimulation test was also performed in two, four and four patients, respectively. All patients had sporadic pituitary adenomas. MEASUREMENTS: Serum CgA was measured using a solid-phase two-site immunoradiometric assay based on monoclonal antibodies that bind to two distinct contiguous epitopes within the 145-245 region of CgA. RESULTS: Mean basal CgA concentration in 14 normal subjects was 80.2 ng/ml (SD: 31.7; range 19-124). A cut-off value for normal range was thus set at 125 ng/ml. TRH injection did not change significantly the CgA levels, peak values remaining less than 124 ng/ml. Three out of 27 subjects with NFPA (11%) had elevated basal CgA levels (576, 143, 241 ng/ml, respectively). Serum levels of CgA were not influenced by TRH in any of the NFPA subjects (including those three with increased basal levels). One out of 15 acromegalic patients (6.6%) and one out of 19 hyperprolactinemic patients (5.2%) had elevated serum basal CgA which did not significantly increase after TRH administration. In the remaining patients TRH-tests did not modify CgA levels. GnRH administration did not modify CgA levels. CONCLUSIONS: CgA serum levels measurement, assessed with a novel assay, does not provide a helpful marker for the clinical management of functioning and NFPA.
OBJECTIVE AND DESIGN: Galectin-3 is a beta-galactoside-binding protein that plays a role in cell adhesion and tumour progression. It was shown recently to diagnose malignant follicular thyroid lesions accurately. The reliability of this marker in the differential diagnosis between medullary thyroid carcinoma and C-cell hyperplasia was studied by immunohistochemistry. PATIENTS: Tissue specimens were obtained from 34 patients belonging to families with medullary thyroid carcinoma who underwent prophylactic thyroidectomy for RET gene mutation and/or abnormally increased plasma calcitonin levels. RESULTS: Galectin-3 was expressed in 23 of 25 cases of medullary thyroid carcinoma and in none of the nine cases of C-cell hyperplasia only, giving a sensitivity of 92% and a specificity of 100% for the diagnosis of carcinoma. A significant association was found between higher galectin-3 expression and occurrence of lymph node metastases (P < 0.05). CONCLUSIONS: Galectin-3 is a reliable diagnostic marker of medullary thyroid carcinoma, and its use may provide relevant information for prognosis and therapy.