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C de Micco

Publications and source records attributed to C de Micco.

At least 19 recordsLinked to original sources
PubMed2003

Specific pattern of RAS oncogene mutations in follicular thyroid tumors.

The prevalence of H-RAS, K-RAS, and N-RAS gene mutations in thyroid tumors according to malignancy and histology is controversial. Differences in methodology and histological classifications may explain discrepant results. To address this issue, we first performed a pooled analysis of 269 mutations garnered from 39 previous studies. Mutations proved significantly less frequent when detected with direct sequencing than without (12.3% vs. 17%). The rate of mutation involving N-RAS exon 1 (N1) and K-RAS exon 2 (K2) was less than 1%. Mutations of codon 61 of N-RAS (N2) were significantly more frequent in follicular tumors (19%) than in papillary cancers (5%) and significantly more frequent in malignant (25%) than in benign (14%) tumors. H-RAS mutations in codons 12/13 (H1) were found in 2-3% of all types of tumors, but H-RAS mutations in codon 61 (H2) were observed in only 1.4% of tumors, and almost all of them were malignant. K-RAS mutations in exon 1 were found more often in papillary than follicular cancers (2.7% vs. 1.6%) and were sometimes correlated with special epidemiological circumstances. The second part of this study involved analysis of 80 follicular tumors from patients living in Marseille (France) and Kiev (Ukraine). We used direct sequencing after PCR amplification of exons 1 and 2 of the three RAS genes. Common and atypical adenomas were separated using strict cytological criteria. Mutations of H1-RAS were found in 12.5% of common adenomas and one follicular carcinoma (2.9%). Mutations of N2-RAS occurred in 23.3% and 17.6% of atypical adenomas and follicular carcinomas, respectively. These results confirm the predominance of N2-RAS mutations in thyroid follicular tumors and their correlation with malignancy. They support the implication of N2-RAS mutations in the malignant progression of thyroid follicular tumors and the assumption that some atypical adenomas are precursors of follicular carcinomas.

Adenocarcinoma, Follicular↗
PubMed2001

Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications.

Despite several recent studies, the biological status and clinical relevance of telomerase expression in tumours derived from the thyroid follicular cell remain controversial. This study has analysed a series of normal, benign, and malignant thyroid samples using two novel approaches: the use of purified epithelial cell fractions to eliminate false-positives due to telomerase-positive infiltrating lymphocytes; and the simultaneous measurement of telomere length to provide a clearer interpretation of telomere dynamics in thyroid neoplasia. The data obtained support the prediction that the epithelial component of non-neoplastic thyroid and of follicular adenomas is telomerase-negative, any positive results being explicable by lymphocyte infiltration. In contrast, many malignant tumours, both follicular and papillary, were telomerase-positive. However, serial dilution of extracts indicated a wide spectrum of activity in these cancers, possibly related to variation in the proportion of telomerase-positive cells. Furthermore, an unexpectedly high proportion were telomerase-negative, a finding which was not explicable by technical problems such as TRAP (telomeric repeat amplification protocol) assay sensitivity. Many of these apparently telomerase-negative tumours had abnormally long telomeres. Correlation of telomerase and telomere length data suggests that thyroid cancers fall into three biological groups: telomerase-positive lesions, consistent with the conventional model of telomere erosion followed by telomerase reactivation; telomerase-negative tumours, which maintain telomere length by a mechanism independent of telomerase; and telomerase-negative tumours which are still undergoing telomere erosion and may therefore be composed of mortal cancer cells. From a clinical standpoint, it is concluded that telomerase detection on unfractionated tissue, such as fine needle aspirates, is of no value as a marker of malignancy in follicular lesions, due to both low sensitivity and specificity.

Adenoma↗
PubMed1997

Interest of routine measurement of serum calcitonin: study in a large series of thyroidectomized patients. The French Medullary Study Group.

The aim of our study was to assess the ability of routine calcitonin (CT) measurement to improve the preoperative diagnosis of medullary thyroid carcinoma (MTC) in nodular thyroid diseases. We systematically determined basal CT in 1167 patients before thyroid surgery and performed a pentagastrin (Pg) CT stimulation test in 121 of these patients whose basal CT level was normal. Sixteen MTC (1.37%) were found on histopathological examination of surgical specimens: 14 in the 34 patients (41.1%) with abnormal basal CT levels and 2 in the 1133 patients with normal basal CT levels (0.17%). An abnormal increase in Pg-stimulated CT was observed in 7 of the 121 patients tested and was related to microscopic MTC in 2 cases. Among 1167 thyroidectomized patients with nodular thyroid diseases, the prevalence of MTC was 1.37% and reached 41.1% when the basal CT level was abnormal (3% of the patients). CT evaluation detected MTC, whereas other procedures, such as fine needle aspiration cytology, failed, thus allowing early radical surgery. CT measurement should thus become a routine part of the diagnostic evaluation of nodular thyroid diseases.

Adolescent↗
PubMed1997

[Anatomo-pathology and histological prognosis of follicular thyroid carcinoma].

After reviewing the classification and main histopathological features of differentiated follicular thyroid carcinoma, characters influencing their prognosis are analysed in light of publications from the last ten years. In all cases distant metastasis, extrathyroid invasion and age are the most significant features; histology, limitation and differentiation are then involved. Lymph node metastasis play a role mainly in the evolution of follicular carcinoma. The diagnosis of malignancy suspected on fine needle aspiration cytology must be confirmed on frozen sections at time of surgery; in the main time extension and histological type can be determined and help to choose the appropriate surgical procedure. The study of biological parameters such as ploidy, DNA content, cellular proliferation or expression of oncogens brings no better information than clinicopathological parameters and has presently no practical interest for the choice of treatment.

Adenocarcinoma, Follicular↗
PubMed1996

[Early diagnosis of sporadic medullary cancers of the thyroid: value of systematic assay of calcitonin].

OBJECTIVE: Sporadic medullary cancer of the thyroid is often diagnosed late beyond the surgically curable stage. The aim of this work was to assess the capacity of routine calcitonin assay as an early diagnosis test for medullary cancer in patients with a thyroid lesion. METHODS: Calcitonin was assayed (normal < 10 pg/ml) as a routine test from 1993-1995 in a series of 2975 patients seen for thyroid exploration. When baseline level was above 10 pg/ml, a pentagastrine test was performed (normal < 30 pg/ml). All patients with a calcitonin peak > or = 100 pg/ml after pentagastrin underwent surgery for suspected medullary cancer. Surgery for suspected malignancy, hyperthyroidism or locoregional functional disorders was also performed in 1494 of the included patients, independent of calcitonin level. Patients with personal or familial history of multiple endocrine disease were excluded. Fine needle aspiration was done in all patients with an unique or predominant thyroid nodule. RESULTS: Medullary cancer of the thyroid was demonstrated in 14 patients (0.47%). Among 8 patients with clinically patent tumor, the diagnosis was established in 3 on the basis of cytology results and elevated calcitonin level; in the 5 other cases, initial cytology was incorrect (anaplastic, papillary, thyroiditis) but correct diagnosis was established on the basis of high calcitonin levels. Diagnosis was suspected preoperatively in the 6 others solely because of high calcitonin; these patients had microlesions measuring 1.2-9 mm. None of the 7 patients with a medullary cancer measuring < 10 mm had node extension at surgery and all 7 attained biological cure. Among the 7 other patients with a lesion > 10 mm, calcitonin level returned to normal level in 3 and remained high in 2; the 2 others died with distant metastasis. CONCLUSION: Routine assay of calcitonin in all patients with a thyroid nodule can improve preoperative diagnosis of medullary cancer of the thyroid and allows early diagnosis of latent infraclinical tumors.

Adult↗
PubMed1996

Immunocytochemical staining with monoclonal antibody MoAb47 in the diagnosis of thyroid neoplasms (preliminary communication).

The study is aimed at the estimation of diagnostic value of immunocytochemical (ICH) staining with MoAb47 of cytological material from thyroid nodules obtained by FNAB with emphasis on a precise distinction between benign and malignant follicular tumours. Monoclonal antibody 47 has very strong avidity to thyroperoxidase (TPO) from normal thyrocytes and from benign thyroid lesions. Binding of MoAb47 with TPO from thyroid carcinoma cells is null or very weak. We report the results of ICH staining in 34 cases of "cold" or quickly growing thyroid nodules, most of them solitary. Cytological diagnosis was thyroid carcinoma in 4 cases, microfollicular neoplasm in 7 and different benign lesions in 23. As expected in carcinomas the ICH staining was negative and the presence of cancer was histopathologically proved in 3 already operated on patients. In all follicular tumours staining with MoAb47 was positive and in 5 surgically treated cases postoperative examination identified benign follicular adenoma. Smears from colloidal nodules, cystic and degenerative lesions stained positively with MoAb47. In our opinion staining of cytological material with MoAb47 may improve the diagnosis of thyroid nodules.

Adolescent↗
PubMed1995

PCR analysis of hepatitis B virus DNA in paraffin-embedded liver tissue from patients with chronic liver disease.

We described a nested polymerase chain reaction protocol to detect hepatitis B viral DNA in paraffin-embedded liver tissue and tried to determine whether this virus was associated with non-B chronic liver disease. Fifty-five samples were obtained from 28 patients with B, and 27 patients with non-B chronic liver disease (35 cirrhosis, 4 hepatocellular carcinoma and 16 chronic hepatitis). The two sets of primers amplify a sequence located in a conserved polymerase/surface region of the viral genome. Reaction products were analysed using a nonisotopic hybridization method. None of the 27 (0%) seronegative samples and 20 of the 28 (71%) seropositive specimens were positive for hepatitis B virus DNA. There were 4 false negatives in which beta-globin PCR was positive. Although its sensitivity is reduced in formalin-fixed paraffin-embedded tissue, nested PCR allows rapid detection of HBV DNA sequences and can be a useful tool if no frozen tissue is available.

Adolescent↗
PubMed1994

[Multiple endocrine neoplasia type I. Review and presentation of the study group of multiple endocrine neoplasia type I (GENEM I)].

Multiple endocrine neoplasia type I, also known as Wermer's syndrome, is characterized by the presence of functioning or nonfunctioning tumors or hyperplasia of the parathyroid glands, pancreatic islet cells and pituitary gland. MEN I syndrome may be either familial or sporadic. MEN I locus has recently been mapped to chromosome 11, and further characterization of the abnormal gene appears imminent. The GENEM I, a multidisciplinary study group is in the process of formation. Pathologists have to specify the morphological criteria of hyperplasia vs tumor. Further characterization of the gene and its product requires the application of molecular biology methods to the pathologic tissues of these patients.

Adrenal Gland Neoplasms↗
PubMed1994

[Malignancy markers in the cytodiagnosis of thyroid nodules. Thyroid peroxidase].

The enzyme thyroid-peroxidase (TPO) possesses in thyroid malignancy an immunological alteration disclosed by an anti-TPO monoclonal antibody termed MoAb47: a negative immunostaining with MoAb47 thus represent a marker of malignancy for thyroid tumors. The present work has been intended to investigate the ability of TPO immunodetection to assist the diagnosis of malignancy in fine-needle aspirates (FNA) of thyroid nodules. The study concerns 300 patients with histologically proven thyroid nodules. The results of TPO immunodetection have been compared to the final histological diagnosis and in 279 cases, to the results of standard cytological analysis. From 248 benign nodules, 215 yielded more than 80% positive cells. All malignant nodules had less than 80% positive cells and most of them less than 40%. According to these results, with 80% positive cells as the threshold between benign and suspicious or malignant results, the sensitivity of the method for the screening of malignancy is 100%, its specificity 86.7% and its overall accuracy 89%.

Antibodies, Monoclonal↗
PubMed1993

Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies.

The presence of thyroglobulin (TG) was investigated by immunohistochemistry with one polyclonal and three distinct monoclonal anti-TG antibodies in 19 primary and 15 metastatic medullary thyroid carcinoma (MTC) cases. In two primary tumors possessing a mixed trabecular and follicular growth pattern, a significant number of tumor cells were positive with the four antibodies in all parts of the tumor; these tumors were considered to be genuine mixed follicular and parafollicular tumors. The 17 other primary tumors looked like "classical" (ie, predominantly compact) MTC. Eight contained tubular or microfollicle-like structures that were consistently TG-negative. Eight contained residual entrapped normal follicles positive with the four anti-TG antibodies. In six cases isolated foci of tumor cells reacted with polyclonal antibody or monoclonal antibody 11. In 10 cases circulating TG stained positively with polyclonal antibody in vascular channels, five cases stained positively for TG with monoclonal antibody 11, four cases stained positively for TG with monoclonal antibody 7, and three cases stained positively for TG with monoclonal antibody 1. In metastases TG was found in tumor cells in only one instance, but positive reactions were obtained in vascular channels and macrophages in several cases. We conclude from this study that there is no genuine secretion of TG in classical, compact MTC, which differs morphologically and functionally from mixed follicular and parafollicular tumors secreting both TG and thyrocalcitonin.

Antibodies, Monoclonal↗
PubMed1993

[Thyroid cytology: evaluation and perspectives].

For the majority of centres worldwide that specialize in the treatment of thyroid diseases, cytology is now the first investigation carried out in patients with thyroid nodules. Procedures and expected results of this examination are described, together with the progress accomplished by immunocytochemical detection of malignancy markers such as thyroid peroxidase (TPO). Puncture biopsy is preferably by fine needle aspiration, the quality of the examination depending essentially on the quality of the specimen and the cytologist's experience. Results are recorded as benign (colloid nodules and thyroiditis), intermediate (microfollicular tumors, doubtful lesions) and malignant (follicular, papillary, anaplastic and medullary carcinomas). In experienced hands, the average sensitivity of the examination for cancer detection is 90 to 95% and its specificity 65 to 75%. These limits result from a non significant level of sampling of 10 to 20% and the persistence of 2 to 5% of false negatives, independent of the cytologist's expertise. Based on results of an ongoing cohort study comprising at present 300 histologically controlled cases, immunodetection of TPO in puncture biopsy specimens using MAb 47 antibodies could result in a sensitivity of about 100% for a specificity of more than 90%.

Biopsy, Needle↗
PubMed1989

Immunology of central nervous system tumors.

With progress in cellular immunology and the development of hybridoma technology, the idea of manipulating host-tumor immune interactions to improve the prognosis of brain tumors has aroused renewed interest. Although no brain tumor-specific antigens have been found, and in spite of the wide antigenic heterogeneity of brain tumor cells, some monoclonal antibodies possessing restricted specificity have been isolated and their potential clinical applications investigated. One of the most pronounced changes in the cellular immune responses of brain tumor patients is a profound depression of the T4-helper lymphocytes. Clinical and laboratory trials are under way to assess the ability of lymphokines, such as gamma-interferon or interleukin-2, to restore immunologic competence in these patients and potentiate a specific anti-tumor immunologic response. Recent work suggests that the endothelium-astrocyte complex may have a pivotal role in assisting the escape of brain tumors from the host's immunologic responses, since it is responsible for the intracerebral sequestration of antigens and local anti-tumor responses. In this review, the data on the antigenic properties of central nervous system tumors and the host's humoral and cellular immune responses to them are analyzed and potential immunologic therapies are discussed.

Antibody Formation↗
PubMed1989

[Immunology of tumors of the central nervous system].

Central nervous system (CNS) tumours possess special immunological features resulting from their development in an organ having a privileged immunological status. The following review gives a summary of actual data concerning their tumour-associated antigens, the immunological responses of their hosts and the mechanisms permitting them to escape from these responses. There is presently no proof of the existence of tumour-specific antigens on spontaneous glial tumours. Much progress has been made in this area with the development of monoclonal antibodies technology which mainly disclosed the profound antigenic heterogeneity of brain tumours. This heterogeneity could favour the escape of brain tumours from immunosurveillance; furthermore, it represents a major limitation to the use of monoclonal antibodies for diagnosis or therapy. Regarding the immunological responses of brain tumour patients, the main feature is a profound depression of cellular immunity creating an anergic state toward a large number of antigens. In vitro, it concerns specifically T4 helper lymphocytes: their mitogenic responses and secretion of interleukin-2 after antigenic stimuli are drastically reduced. Three phenomena have also been incriminated to explain the defect of immunosurveillance in brain tumour patients: 1) the synthesis by tumour cells of a protective mucopolysaccharidic coat, 2) the secretion by these cells of specific immunosuppressive factors related to cytokines, 3) the isolation of CNS maintained by the blood-brain barrier which regulates the circulation of immunocompetent cells between the intra- and extracerebral compartments. Currents efforts are focused on the individualization of therapy based on these biologic principles.

Antibodies, Monoclonal↗
PubMed1988

[The immune status of the central nervous system].

The central nervous system (CNS) has no true lymphatic outflow and is protected by the blood-brain barrier. It shares special relationships with the immune system. Though heterologous grafts can sometimes survive inside the brain, explaining that it has been considered as an immunologically privileged site, the CNS is able to generate immunological immune reactions and can exert a regulatory role on the extracerebral ones. Inside the brain, the immunological reactions are probably due to populations of immunocompetent cells and potentially macrophagic cells which are there permanently but in an inactivated state. Nevertheless the first event triggering these reactions and responsible for the activation of immunocompetent cells remains highly hypothetical. The astrocyte-endothelial cells complex which is the anatomical support of the blood-brain barrier probably plays a vital role in this process. Permanent exchanges between the CNS and the immune system are assumed by soluble mediators: lymphokines, neurotransmitters and hormones. These allow the CNS to control to some extent the extracerebral immunological reactions by feed-back regulation mechanisms.

Animals↗
PubMed1987

Immunohistochemical study of thyroglobulin in thyroid carcinomas with monoclonal antibodies.

The effectiveness of an immunoperoxidase technique using four monoclonal antibodies (mAb) is compared to a technique using one polyclonal antibody (pAb) to detect human thyroglobulin (Tg) in paraffin sections of 55 thyroid carcinomas. With the pAb, a positive reaction was found in 82% of the cases. With the four mAb, the presence of Tg was demonstrated in 96.5% of the cases. The mAb gave better results than the pAb on poorly differentiated and anaplastic thyroid carcinomas. Many of the thyroid carcinomas in this study, especially the poorly differentiated and anaplastic type, failed to react with all four mAb to Tg. These results confirm the notion of the heterogeneity of Tg in thyroid carcinomas and indicate that a battery of carefully selected mAb can be successfully used for routine histopathologic detection of Tg in these tumors.

Adenoma↗
PubMed1986

Role of the blood-brain barrier in the establishment of the immune response against polyoma virus-induced cerebral tumours in hamsters.

The existence of an immunological blood-brain barrier (BBB) is well established but its role in cerebral tumour immunology is less well defined. Attempting to clarify this problem we tested the graft rejection of polyoma virus-induced central nervous (CNS) tumours in hamsters after systemic or intracerebral immunization with polyoma virus. Animals were immunized by intracerebral or subcutaneous inoculations of polyoma virus before tumours were induced by intracerebral or intramuscular graft of polyoma-transformed hamster neuroglial cells. The growth of cerebral and muscular tumours was significantly inhibited in animals immunized subcutaneously. In animals immunized intracerebrally the inhibition of growth was highly significant for cerebral tumours and only very slight for intramuscular tumours. These results suggest that the blood-brain barrier allowed immunocompetent effector cells to penetrate inside the CNS but prevented the locally elicited cell-mediated immune response from diffusing outside the CNS. The ability of the brain to develop a local immune response and the partial lack of circulation of immunocompetent cells to cross the BBB could be mainly responsible for the special immune status of the CNS and may greatly interfere with the establishment of an efficient immune response toward brain tumours.

Animals↗