Search PubMed⌕ Search

Biomedical subjects

C De Micco

Publications and source records attributed to C De Micco.

At least 37 records · Page 2Linked to original sources

Thyroid peroxidase immunodetection as a tool to assist diagnosis of thyroid nodules on fine-needle aspiration biopsy.

In a previous work we have reported the presence in 96.9% of malignant and 4.2% of benign thyroid tumors of an immunological abnormality of the enzyme thyroid peroxidase, impeding the fixation of the anti-thyroid peroxidase monoclonal antibody termed "MoAb47". The present study has been designed to establish the ability of thyroid peroxidase immunodetection to assist the diagnosis of malignancy in fine-needle aspiration of thyroid nodules. The fixation of anti-thyroid peroxidase monoclonal antibody was investigated by immunohistochemistry on fine-needle aspirates of 150 surgically removed thyroid nodules (20 papillary carcinomas, five follicular carcinomas, 90 colloid adenomas, nine fetal adenoma, 13 atypical adenomas, five oncocytic adenomas, six Hashimoto's thyroiditis and two Graves' disease). The percentage of positive cells has been compared to the final histological diagnosis. In samples from 113/125 benign nodules 80-100% cells presented a positive immunoreaction, whereas all samples from malignant tumors yielded less than 80% positive cells. Benign nodules exhibiting less than 80% positive cells corresponded to three degenerative colloid nodules, five atypical follicular adenomas, two oncocytomas and two thyroiditis. According to results obtained in this series, with the value of 80% as the limit for discrimination between benign and high-risk nodules, the sensitivity of thyroid peroxidase staining for diagnosis of malignancy would be 100%, its specificity 90% and its overall accuracy 92%. Thyroid peroxidase staining with monoclonal antibody MoAb47 on fine-needle aspirates is a useful adjunct to conventional cytology for the investigation of patients with thyroid nodules.

Biopsy, Needle↗

Fine-needle aspiration of thyroid follicular neoplasm: diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47.

BACKGROUND: We previously demonstrated that thyroid peroxidase (TPO) immunocytochemistry with monoclonal antibody 47 can help to differentiate benign (staining score, 80% or more) from malignant (staining score, less than 80%) thyroid nodules on fine-needle aspiration (FNA) samples. In the present study we assessed the use of TPO immunocytochemistry in the cytologic diagnosis of thyroid follicular neoplasms. METHODS: A total of 109 histologically proven follicular tumors were studied. There were 60 microfollicular adenomas, 23 atypical adenomas, 17 oncocytic adenomas, and 9 follicular carcinomas. Adequate preoperative FNA samples were available in all cases. TPO immunocytochemistry was performed on one half of the slides. RESULTS: The staining score was less than 80% in all follicular carcinomas, whereas it was 80% or more in 68 of 100 benign tumors. There was no false negative and 32 false positives for diagnosis of malignancy. The false positives were 10 microfollicular adenomas, 13 atypical adenomas, and 9 oncocytic adenomas. TPO immunocytochemistry has a sensitivity of 100% and a specificity of 68% for screening of follicular cancer. CONCLUSIONS: TPO immunocytochemistry with monoclonal antibody 47 on FNA samples is a highly sensitive and fairly specific method to distinguish benign from malignant follicular neoplasms. This technique can help to reduce the number of surgical procedures for benign thyroid nodules without increased risk of overlooking malignancy.

Antibodies, Monoclonal↗

Significance of thyroglobulin antibodies cross-reactive with thyroperoxidase (TGPO antibodies) in individual patients and immunized mice.

Thyroglobulin (TG) and thyroperoxidase (TPO), both involved in thyroid hormone synthesis, represent major autoantigens in thyroid autoimmune disease. Despite numerous studies, the emergence, pathophysiological significance and role of autoantibodies to TG and TPO remain elusive. The recent identification of a new category of thyroid-specific autoantibody interacting with both TG and TPO (TGPO autoantibodies) offers a new opportunity in the study of thyroid autoimmunity. To gain a better insight into the significance of these TGPO autoantibodies, measurement in individual samples appeared necessary. The unique property of TGPO autoantibodies, simultaneous binding to TG and TPO, was used to set up a sandwich method which combined coated TG and radio-iodinated TPO. This method was found to be strictly specific for TGPO autoantibodies and sensitive enough to assay TGPO autoantibodies in serum. In humans, TGPO autoantibodies were found in most of the sera with high TG and TPO autoantibody titres, but not in sera negative for TG autoantibodies, whatever the TPO autoantibody titre. Furthermore, high TGPO autoantibody titres were found in sera strongly cytotoxic for cultured porcine thyroid cells. However, significant correlation of TGPO autoantibody titre was observed neither with TG and TPO autoantibody titres (n = 48) nor with complement-dependent cytotoxicity (n = 50). TGPO antibody assay was also performed in individual plasma of CBA/J mice immunized with either human TG (n = 6) or human TPO (n = 6). Immunization with TG induced high levels of not only TG but also TGPO antibodies, which exhibited a strong reactivity for TPO and whose binding to TG and TPO was fully inhibited by TG. In contrast, immunization with TPO induced high levels of only specific TPO antibodies accompanied by low levels of specific TG antibodies. In this case TGPO antibodies were not detected. Of note, TG- and TPO-immunized mice mounted an immune response against their own TG, but did not exhibit histological signs of thyroiditis. Large panels of TG and TPO MoAbs were also investigated with this method: 18/25 TG MoAbs and only 1/13 TPO MoAbs were found cross-reactive. Taken together, these data provide evidence that TGPO antibodies are effectively present in individual patients and TG-immunized mice, are different from specific TG and TPO antibodies, and may derive from natural B cell repertoire by autoimmune processes involving TG and not TPO.

Animals↗

Immunohistochemical study of thyroid peroxidase in normal, hyperplastic, and neoplastic human thyroid tissues.

An immunohistochemical study using two monoclonal antibodies (MoAb 30 and MoAb 47) against thyroid peroxidase (TPO) was performed on surgical specimens of human thyroid carcinoma (n = 65), adenoma (n = 70) and Graves' disease (n = 10). Normal adjacent thyroid tissue was used as positive control. Monoclonal antibody 30 reacted significantly with all adenoma and most carcinoma, whereas MoAb 47 reacted with 66 adenoma but only two carcinoma. Of the four adenomas that did not react with MoAb 47, three were of the fetal type. Both carcinoma reacting with MoAb 47 were of the well-differentiated follicular type. These findings further confirm the hypothesis that thyroid carcinoma is associated with changes in the quantity and antigenic properties of TPO. Although the alterations in antigenic behavior revealed by MoAb 47 are not 100% specific, they may allow more accurate diagnosis of malignancy in thyroid tumors.

Adenocarcinoma↗

[Anatomo-pathology of cholesteatoma].

The authors, from their own histopathological studies and from an overview of otological literature focus the controversial problems about the so-called disease cholesteatoma. The history of cholesteatoma has been marked out by pathologic data which, initially caused the cholesteatoma to be identified as a keratinized squamous tumor. This misnomer will however be retained because of it long-established usage. "Skin in the wrong place" in the middle ear summarizes this clinical entity. Electron microscopic observations provide arguments in favour of the migratory theory and the invasion of the epidermis from the bottom of the external ear canal into the middle ear cavity (identical fine morphology between skin and cholesteatoma, presence of Langerhans and Merkel cells, sharp junction between the advancing front of the cholesteatoma and the middle ear mucosa). Recent immunohistological techniques allow consideration of cholesteatoma as a self-induced inflammatory process in response to tissular and cellular conflicts. A cholesteatoma could be merely a non-healing wound process and a disease of epidermal growth control occurring in the middle ear space. The logical principles governing cholesteatoma surgery, suggested by these biological considerations, are: total removal of cholesteatoma matrix, prevention of cholesteatoma recurrence by a careful respect of the barrier separating the middle ear mucosa from the skin-lined bony external ear canal, maintenance of good healing conditions for both mucosa in a closed well-ventilated middle ear and epidermis in a harmonious anatomical external canal.

Cell Movement↗

[Differentiated thyroid carcinoma of follicular origin: new data in 1988].

The problems raised by the histologic diagnosis and prognostic evaluation of differentiated thyroid carcinomas developed from follicles (DTCs) have significantly changed over recent years, partly as a result of the development of medical data processing and immunodetection techniques. From the body of current data, the following fundamental points emerge. First, the importance of factors that influence the course of these tumors can be accurately assessed only through computer-performed multifactorial statistic studies. The main prognostic factors include age, tumor spread at the time of diagnosis, and histologic features. Essential histologic features include demarcation of tumors and degree of differentiation. Second, differential diagnosis between papillary and follicular carcinomas, based primarily on cytologic criteria, may prove difficult. The usefulness of this distinction is even challenged occasionally. The value of cytokeratin immunodetection for distinguishing these two tumor types is discussed. Third, it may be impossible to ascertain the malignity of highly differentiated follicular tumors. No truly significant marker for malignity has been identified to date. The decision must therefore be reached by the cautious use of histologic criteria, including cytologic and architectural features, none of which is diagnostic per se.

Adenocarcinoma↗

Thyroid peroxidase is the organ-specific 'microsomal' autoantigen involved in thyroid autoimmunity.

Autoantibodies (aAb) in serum of patients with autoimmune thyroid diseases (AITD) are directed to an antigen associated with thyroid microsomes. Although it has been investigated over almost three decades, the nature of this autoantigen remained unknown. Taking advantage of monoclonal antibodies (mAb) produced in our laboratory, we have demonstrated that thyroid peroxidase (TPO) is the 'microsomal' antigen. Sera of patients with AITD strongly inhibited the binding of only one of 19 mAb raised against human thyroid plasma membranes. This mAb did not react with thyroglobulin but achieved significant binding to preparations of human, bovine and porcine TPO, bovine lactoperoxidase and human myeloperoxidase without altering the enzyme activity. The mAb has been used to immunopurify the human TPO from solubilized thyroid microsomes. The procedure allowed high purification (approximately 3500-fold) of the native enzyme with a reasonable yield (approximately 10 mg TPO/kg thyroid tissue). Human TPO exhibited a specific activity of 350-400 guaiacol U/mg, a peak in the Soret region and a ratio of A411 nm to A280 nm of 0.20-0.25. Upon SDS-polyacrylamide gel electrophoresis, the purified enzyme gave two contiguous bands in the 100 kDa region. Performed in non-reducing conditions, electrophoresis of TPO showed one band in the same 100 kDa region. Sera with aAb to the microsomal antigen immunoprecipitated purified TPO to an extent ranging from 80 to 100% of the initial enzyme amount while sera from normal subjects or from patients with undectable level of anti-microsomal aAb elicit a decrease of less than 30% of the total TPO activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Quantification of thyroglobulin messenger RNA by in situ hybridization in differentiated thyroid cancers. Difference between well-differentiated and moderately differentiated histologic types.

Thyroglobulin messenger RNA (mRNA) was located and quantified in tissue sections of differentiated human thyroid cancers by in situ hybridization using cloned complementary DNA probes. The cells of the well-differentiated follicular and papillary forms contained similar levels of thyroglobulin mRNA, corresponding to about 2000 copies per cell. In contrast, cells of moderately differentiated thyroid cancers contained about two to three times less thyroglobulin mRNA. It was also found that thyroglobulin mRNA was present almost exclusively in polyribosomes under the form of heavy polyribosomes actively synthesizing thyroglobulin. It is suggested that in situ hybridization method allows localization of specific mRNA in differentiated thyroid cancers and correlation with the level of differentiation of the cells.

Autoradiography↗

[Enteropathy due to clofazimine treatment. A case report with an ultrastructural study].

The authors report a case of enteropathy due to clofazimine treatment for prurigo nodularis. The drug usually restricted to the treatment of leprosy has sometime been given to patients suffering from skin diseases because of its assumed anti-inflammatory effects. When high dosage of clofazimine treatment is carried on during a long period, and drug accumulates in the tissues and precipitates as a solid. This crystal storage in the lamina propria of the jejunal mucosa and in the mesenteric lymph nodes accounts for an enteropathy, sometime severe but slowly regressing after drug withdrawal. The electron microscopic study shows the prints of these crystals in autophagic vacuoles of histiocytes.

Clofazimine↗