Biomedical subjects
Publications and source records attributed to C Calmettes.
Abnormal levels of calcitonin and carcinoembryonic antigen in plasma, and detectable amounts of these markers in tumours are not restricted to typical forms of medullary cancer of the thyroid but are also characteristic of some other tumours of the gland. The diagnosis of these tumours, therefore, should not rely entirely on histological findings but should include a search for specific biochemical markers in plasma and tissues.
Thirty-one patients were studied to evaluate the prognostic value of both calcitonin (CT) and CEA levels determined after the initial treatment in medullary thyroid carcinoma (MTC). Twenty-seven patients were evaluated three to nine months after initial treatment and four others afterwards. The CT and CEA levels were significantly higher and the survival rate lower in the eight patients with residual clinical disease as compared to the 19 patients in complete clinical remission. In patients in complete clinical remission, 11 had elevated CT level after treatment, and all had initial lymph node involvement. Five of these 11 relapsed and one died. None of the eight patients with normal CT levels after treatment relapsed. CEA levels were always abnormally high when patients relapsed. Fourteen patients in complete remission with high CT levels were followed for more than four years. Six had normal CEA levels and no relapse was observed. Eight of the 14 had pathological CEA levels and six of eight relapsed: five of these six patients presented CEA elevation from six to 36 months before the clinical relapse. In two of these six patients, a venous catheterization sampling method demonstrated infra clinical local recurrence. In two patients with liver metastases, the time course changes of CT and CEA levels were different and CEA appeared to be a more sensitive tumor marker than CT. These data are consistent with previous data concerning the values and limits of CT level for the management of MTC. Furthermore, this study demonstrates the prognostic significance of CEA determination in MTC. CEA appears to be a sensitive selective tumor marker capable of defining a high-risk subgroup.
Previous studies have shown that certain patients suffering from poorly differentiated follicular carcinoma (PDFC) of the thyroid had high levels of calcitonin (CT) and carcinoembryonic antigen (CEA) in the plasma. In this work, both CT and CEA were localized in tissue sections obtained at operation from patients suffering from PDFC. The results confirm the hypothesis that certain cases of PDFC are in fact CT-secreting tumors and represent another type of thyroid neoplasma. Patients suffering from PDFC should be screened using both CT and CEA assays.
An immunohistochemical and electron microscopy study has allowed us to find in a human thyroid cancer, follicle differentiation associating in a characteristic architectural pattern C cells, ciliated cells and follicular cells. Ultrastructural features were similar to those described in the normal adult Mouse thyroid by Wetzel and Wollman [1] and interpreted by them as a second type of thyroid follicle of ultimobranchial origin. The discovery of these structures within metastatic lymph nodes excludes normal thyroid follicle contamination. The presence of these neoplastic structures lead us to make the hypothesis of a stem cell of ultimobranchial and endodermal origin common to all the cells described.
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Carcinoembryonic antigen (CEA) and calcitonin (CT) were extracted from medullary carcinoma of the thyroid (MCT) tissues, fractionated on Sephacryl S-200 and chromatographed on Concanavalin A. CEA purified from MCT is closely related to CEA extracted from colonic tumors. It has an equivalent molecular weight, is a glycoprotein and has a similar electrophoretic mobility in both SDS and basic polyacrylamide electrophoresis. A certain degree of heterogeneity is present in the form of a smaller molecular weight component. Large molecular forms of CT which are present in MCT tissues and which co-elute with the minor component of CEA on Sephacryl chromatography can be separated by Concanavalin A chromatography.
Medullary carcinoma of the thyroid (MCT) is characterized by high circulating levels of calcitonin (CT) and of carcinoembryonic antigen (CEA), these markers enable the diagnosis of the tumour, the assessment of the efficacy of treatment and the detection of metastases at a subclinical stage. In 130 patients with a primary tumour and/or metastases, CT level was high. In 120 of them (92%), CEA level was also high. There was a positive correlation between levels of CT and of CEA, and both assays should be included in the preoperative examinations. Following removal of the tumour, normalisation of CEA levels takes several weeks, in contrast to CT where normalisation is rapid. Finally, these estimations may be used to detect familial forms at a subclinical stage. This enabled us to detect 16 new cases of MCT amongst 77 subjects studied.
An immunohistological study of five cases of medullary carcinoma of the thyroid was undertaken with monospecific antisera against CEA and NCA. CEA was present in different areas of the tumors: cell cytoplasm, cell membrane at its apical pole when the tumor had a pseudoglandular organization, deposits in the lumen of pseudoglands, and peri- and extra-cellular deposits. From these extra-cellular deposits, CEA could easily reach the circulation, thus causing rising serum levels up to high values. NCA was found in the same tumors and in the same localizations.
Cross reaction studies using radioimmunoassays specific for human and porcine calcitonin showed that rabbit calcitonin is structurally more closely related to human than to porcine calcitonin.
Radioimmunological assays of peptidic hormone levels is now an essential procedure for the diagnosis of polyadenomatosis. The diversity of pathological associations found in polyadenomatosis cannot be completely explained by the unitary theories that have been proposed. Neither the APUD system, nor the common embryonic origin, nor the reduction in calcitonin excretion can fully explain the clinical picture: a logical explanation has still to be discovered. In practice, ectopic secretions are frequent in type 2 polyadenomatosis (medullary cancer, pheochromocytoma, neurofibroma, Marfan's syndrome, hyperparathyroidism) contrary to what is observed in type 1 cases (pituitary, parathyroid, pancreas).
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Hypercalcaemia always results in serious clinical sequalae and, if not treated, carries a most unfavourable prognosis. The clinician will gain major diagnostic help from an evaluation of the calcitonin and parathyroid hormone blood levels. With regard to parathyroid hormone we have developed, for the first time, a radioimmunoassay which is specific for the estimation of biologically active hormone in the circulation. We are dealing here with an unusual radioimmunological situation as the immunochemical sites are generally quite distinct from those associated with hormonal activity. We are presenting in this first paper the normal values and also the variations that occur in different types of hypercalcaemia. The comparison of these results with those obtained by the usual methods of estimation for parathyroid hormone assay lacking in biological activity shows the value of this new technique.
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The localization of intracellular calcitonin has been achieved by immunofluorescence in the cytoplasm of all cells forming the epithelium of the ultimobranchial body of eels, using a human antiserum against synthetic Salmon calcitonin I. The specificity of the reaction is demonstrated by inhibition with synthetic salmon calcitonin (S.C.T.); the fluorescence is not inhibited by synthetic human calcitonin (H.C.T.).
We have detected high values of carcinoembryonic antigen in the blood of patients suffering from medullary carcinoma of the thyroid (MCT). Levels of the antigen and calcitonin, the hormone which is specifically secreted by these tumours, are positively correlated. Stimulation of calcitonin secretion has no effect on carcinoembryonic antigen levels. Though the antigen assay is non specific for MCT, it may improve the diagnosis and follow-up of MCT-patients.
The authors report a case of probably ectopic secretion of calcitonin in a 35 year old woman suffering from a malignant tumour in a double intra- and extra-spinal form. Hormone levels returned to normal after complete excision of the tumour, in which it was impossible to demonstrate the presence of calcitonin despite a very marked secretory appearance by electron microscopy. Study of the literature concerning the secretion of calcitonin by malignant tumours indicates the high degree of contradiction concerning the origin and the significance of increased radio-immunological levels of this hormone, which it is not possible to use without criticism as a "marker" of carcinomas.