Search PubMed⌕ Search

Biomedical subjects

S Sciacchitano

Publications and source records attributed to S Sciacchitano.

28 records · Page 2Linked to original sources

Estrogen receptors: new perspectives in breast cancer management.

The imbalance between proliferative and differentiative estrogenic effect, caused by quantitative and qualitative alteration of the estrogen receptor (ER) expression, may play a determinant role in mammary neoplastic transformation. Our studies demonstrate that ER levels are significantly higher in human mammary neoplastic tissues when compared to perineoplastic tissues and that increased ER expression is associated with ER gene hypomethylation. During progressive multifactorial carcinogenesis, ER overexpression may represent an early step in neoplastic transformation. In fact, high levels of ER represent good markers of differentiation and can predict the likelihood of benefiting from anti-estrogen therapy. Nevertheless, about 35% of ER-positive breast cancers are resistant to endocrine therapy and 10% of ER-negative tumors behave as hormone-sensitive tumors. Recent studies on ER mRNA variants, which naturally occur in human breast tumors, demonstrated mutations, deletions and alternative splicings, yielding deletions of exons 3, 4, 5 and 7. ER variants exhibited altered functions or changed the responsiveness to hormonal therapy. Analysis of these variants could be a useful parameter to better predict tumor responsiveness to anti-estrogen therapy. Recently, a regain of hormonal responsiveness by ER-negative breast cancer cells has been reported following ER gene transfection. However, estradiol treatment inhibits rather than stimulates cell growth as well as the metastatic and invasive potential of the ER gene transduced cells. Transfer of the ER gene may be considered as a new therapeutic approach in the management of hormone-independent breast cancer.

Breast Neoplasms↗

Analysis of adenomatous polyposis coli gene in thyroid tumours.

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma.

Adenomatous Polyposis Coli↗

PCR amplification and analysis of ras oncogenes from thyroid cytologic smears.

Fine needle aspiration (FNA) cytology represents a reliable diagnostic procedure for preoperative identification of thyroid carcinoma. For improving its diagnostic accuracy, a technique that allows the analysis of cancer-related gene abnormalities on thyroid FNA smears has been developed. Cells were collected by scraping from thyroid smears, DNA-extracted and ras proto-oncogene sequences amplified by the polymerase chain reaction (PCR). Preliminary destaining of cytologic smears was essential for efficient PCR amplification. Twelve thyroid FNA cytologic smears, characterized by the indeterminate pattern of follicular neoplasia, were analysed for the presence of ras mutations known to confer an oncogenic potential. The same nucleotide substitution at codon 12 of the H-ras proto-oncogene was detected in two different thyroid nodules among six cases that, at final histology, were identified as follicular carcinomas. No ras mutations were observed in the remaining six cases that were diagnosed as follicular adenoma at histologic examination. Molecular analysis of FNA smears may provide additional information on the nature of the lesion underlying thyroid neoplasia, thus improving diagnostic accuracy of conventional FNA cytology.

Adolescent↗

[The thyroid nodule. Diagnostic considerations].

Thyroid nodule is extremely common. Its prevalence has been estimated to be more than 5% in the adult population. If thyroid nodule is a rare condition, 0.004% a year, identifying those nodules, which are likely to be malignant, is very important for physicians. The evaluation of thyroid is carried out using the fine needle aspiration biopsy (FNAB), the ultrasonography, and scanning with 131I and 99Tc. Before FNAB thyroid scans was the most common test in clinical evaluation of thyroid nodules, used to identify "hot" and "cold" lesions. Hot or warm nodules, about 5%, are seldom malignant, whereas cold or hypofunctional have a 10% to 25% chances of being malignant. FNAB is the elected laboratory test: this procedure is easily, simple, non traumatic, and very acceptable to the patients. Ultrasound is useful in several settings: it provides a non invasive and relatively inexpensive means of following the size of nodule, after medical therapy and FNAB.

Adult↗

[The autonomous nodule. Clinical aspects].

Autonomously functioning thyroid nodule (AFTN) includes a wide spectrum of unique or multifocal diseases, either hyper or euthyroid, which share the same independence from thyroid stimulating hormone (TSH) regulation in terms of growth and function. The pathological basis and the recent molecular implications of the disease are briefly discussed. Clinical and epidemiologic data of 1572 patients with AFTN, out of a population of 14107 patients with thyroid diseases, sequentially evaluated from 1974 to 1992, have been retrospectively examined. The mean age of AFTN occurrence is 41 years and it appears more frequently in women (F/M = 5.3/1). Clinical hyperthyroidism occurs only in 17% of patients and is more frequently observed in men over 40 years of age. The presence of sonolucent area inside the nodule is detectable in 8.6% of cases and may be associated with spontaneous arrest of growth. When AFTN is submitted to cytologic evaluation, patterns similar to those observed in nodular goiter are shown (colloid lesion, cyst and nodular hyperplasia). Signs of hyperactivity are also shown by follicular cells. In the presence of a cyst, a fine needle aspiration was performed and a complete resolution was observed in 40% of cases. When cyst recurred after aspiration, a solution of tetracycline was inserted into the cavity. Sclerosing therapy was efficient in evacuating the volume of the nodule in 50% of the cases. Patients with AFTN were followed for a mean period of 61 months and 84.7% of them did not show any morphological or functional change, while the remaining 15.3% of cases became hyperthyroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An introduction to benign thyroid disease: pathophysiologic, epidemiologic aspects and diagnostic methodology.

The role of preoperative noninvasive diagnostic procedures in the management of benign thyroid diseases is critically reviewed and on the basis of a series of more than 13,000 thyroid nodules, sequentially examined, the role of preoperative fine needle aspiration (FNA) cytology in discriminating benign from malignant lesions, is assessed. Retrospective studies were performed to determine the diagnostic accuracy of FNA adopted as routine preoperative screening procedure as compared to intraoperative frozen section (FS) analysis. US-guided FNA was shown to be more accurate allowing the preoperative identification of occult or minimal carcinoma: in fact about 3% of malignant thyroid nodules were detected. Moreover, the operation time is reduced, and unnecessary surgical treatments for benign lesions are eliminated, preventing the need of two-stage cancer surgery. FNA is a cost-effective diagnostic tool with about 20% reduction in the cost of care of patients with thyroid nodules. Most recent methods of molecular biology which seem promising in thyroid tissue sampled by FNA to detect malignant lesions missed by conventional cytology and included in the generic category of "follicular proliferation", are analyzed.

Biopsy, Needle↗

Hyperthyroidism with concurrent thyroid cancer.

The occurrence of thyroid malignancy is considered a rare event in hyperthyroid patients. With the aim of assessing the clinical relevance of this association, we have analyzed the incidence of thyroid cancer in hyperthyroid patients treated by surgery. The incidence of thyroid cancer was retrospectively evaluated in 202 hyperthyroid patients who underwent thyroidectomy during a twenty-year period. A thyroid cancer was diagnosed in 12 cases (5.9 per cent). Histologic examination revealed the presence of papillary carcinoma in 9 cases, follicular carcinoma in 1 case and Hürthle cell carcinoma in 2 cases. The association between thyroid cancer and hyperthyroidism was more frequent in toxic adenomas (17.8 per cent) than in toxic diffuse (5.3 per cent) or multinodular goiters (1.7 per cent). In 8 patients they presented as an occult carcinoma (maximum diameter below 1 cm), but unfavourable histologic features, such as local invasiveness and multifocality, were found in 5 of them. Follow-up data indicate that all 12 patients are currently alive and apparently free of disease. Hyperthyroid patients, particularly those affected by toxic adenomas, should be carefully evaluated to exclude the presence of concurrent malignancy. A special attention should be made moreover to the presence of "occult" lesions that, in our study was characterized in a higher proportion (62.5 per cent) of cases, by unfavourable histologic features.

Adult↗