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Is agNOR and DNA ploidy analysis useful for evaluating thyroid neoplasms?

OBJECTIVE: To correlate the subjective AgNOR counting method and DNA content with histologic diagnoses of thyroid cancer and invasion. STUDY DESIGN: Eighty-one consecutive cases of thyroid carcinoma were selected for DNA and AgNOR analysis. The diagnoses were: papillary carcinoma (n = 40), follicular carcinoma (n = 31), Hürthle cell adenocarcinoma (n = 4), and undifferentiated carcinoma (n = 6). Seven normal thyroids were used as controls. DNA quantitative measurement was performed with Vidas 2.0 software (Kontron Bildanalyse, Munich, Germany) connected to an MPM 210 photometer microscope (Carl Zeiss, Oberkochen, Germany). The DNA index was obtained using histograms. Counting the NORs was performed by subjectively counting the NORs in 200 malignant cells. RESULTS: DNA ploidy analysis showed all Hürthle cell adenocarcinomas, 21 (67%)follicular tumors, 23 (57%) papillary tumors and 4 (67%) undifferentiated carcinomas to be aneuploid. DNA analysis correlated with histologic type of the tumor (p = 0.032). There was no statistical significance to the AgNOR counting variables studied. Statistical analysis showed correlation between ploidy and histologic diagnosis, but not AgNOR counting, to have prognostic value. CONCLUSION: DNA ploidy is more useful than subjective counting of NORs as an adjunct method for thyroid lesion analysis.

Adenocarcinoma, Follicular↗

Phosphofructokinase in normal thyroid tissue and thyroid neoplasms.

Phosphofructokinase (PFK; ATP: D-fructose-6-phosphate transferase, EC 2.7.1.11) was studied in human thyroid carcinomas (n = 16), follicular adenomas (n = 31) and normal thyroid tissue (n = 19). The specific activity in carcinomas (0.129 +/- 0.070) is significantly increased (p less than 0.001) in comparison with phosphofructokinase in normal thyroid tissue (0.028 +/- 0.009). No difference in phosphofructokinase activity seems to exist between follicular, papillary and undifferentiated carcinomas. Specific activities of follicular adenomas are rather heterogeneous. When these tumors were divided into three groups of increasing proliferative activity as judged by histopathological criteria, highest specific activities of phosphofructokinase were found in the group with the highest proliferative activity. The latter group resembles the enzyme activities found in carcinomas. On the other hand specific enzyme activities of the least active tissues were comparable to normal and different from carcinomas. Adenomas show the same isozyme composition as found in normal thyroid tissue. All three isozymes of PFK, M-(muscle)type, L-(liver)type and P-(platelet)type, were present. Phosphofructokinase from papillary carcinomas show a lesser degree of precipitation with anti-M antibodies. A higher amount of platelet type isoenzyme is found in papillary carcinomas compared to follicular and undifferentiated carcinomas. The influence of citrate, an inhibitor of phosphofructokinase, is in agreement with the isozyme composition.

Adenoma↗

[Lymphocytic infiltration in thyroid neoplasms. Preliminary prognostic assessments].

INTRODUCTION: It is known that the immune system is involved in several thyroid diseases and in the reaction against cancer progression. We have therefore evaluated lymphocytic infiltration in the slices of surgically removed thyroids in patients affected by thyroid carcinomas, to further clarify the anatomic and clinical characteristics of this pathology and the possible prognostic correlations. MATERIALS AND METHODS: Thirty-eight patients, 7 men and 31 women, aged 23-73 years, were studied. They underwent total or subtotal thyroidectomy for thyroid carcinoma. The histopathological findings were: papillary carcinomas (P): 22 cases; follicular carcinomas (F): 10 cases; undifferentiated carcinomas (U): 3 cases; other types (e.g., medullary carcinoma, M): 3 cases. RESULTS: The lymphocytic infiltration was evaluated in 4 different grades. The following results, regarding the different histological types, were found: grade 0 (no lymphocytic infiltration) in 10 cases (6 P, 2 F, 1 U, 1 mixed); grade 1 (poor lymphocytic infiltration, equivalent to a non specific inflammatory reaction) in 21 cases (11 P, 6 F, 2 U, 1 M); grade 2 (moderate lymphocytic infiltration) in 4 cases (2 P, 2 F); grade 3 (plentiful lymphocytic infiltration) in 3 cases (2 P, 1 trabecular carcinoma). In 3 patients a lymphocytic (Hashimoto's) thyroiditis was also present. The follow-up, 2 years after surgery, showed, among 17 patients examined, local recurrence and/or lymph node localization in 8 cases (the lymphocytic infiltrations was: grade 1: n = 6; grade 0: n = 2; no one exhibited a higher grade) and apparent remission in 9 (grade 3: n = 2; grade 2: n = 1; grade 1: n = 6; no one exhibited a grade 0 lymphocytic infiltration). DISCUSSION: In most patients a poor or absent infiltration was found. In 7 cases, however, the infiltration was moderate or high. In our experience, no correlation between the histologic type and the infiltration grade was observed. However, in no patient with recurrence of neoplasia a relevant (grade 2-3) infiltration could be observed; patients without recurrence often showed a grade 2-3 infiltration, and no one of them showed a grade 0. The significance of lymphocytic infiltration in thyroid carcinoma is not well clarified. In fact, a few studies underline a possible unfavourable role, since a relevant infiltration seems to be associated with a weak cell-mediated immunity, mostly in follicular and anaplastic carcinomas. However, most data support the hypothesis that the lymphocytic infiltration is a good prognostic feature: in fact, it can be often found in papillary carcinomas and in juvenile thyroid carcinomas, both characterized by a good long-term prognosis. CONCLUSIONS: Our preliminary data underline the opportunity of comparing the clinical course of the disease, the histologic grading and the tumour staging with the lymphocytic infiltration grade, an easily available pathologic datum, for a better prognostic evaluation of patients.

Adult↗

[Thyroid neoplasms in some regions of Russia after radiation accident in Chernobyl].

There is an increase of thyroid carcinoma incidence in regions contaminated after the Chernobyl accident as well as in Russia on the whole. The most considerable increase occurred in younger age groups of population. No difference in thyroid tumors structure was found in polluted with radionuclides and non-polluted regions.

Humans↗

TSH receptor status of thyroid neoplasms--TaqMan RT-PCR analysis of archival material.

Regulation of thyroid follicular cell proliferation and function is mediated by the interaction of TSH with its receptor (TSHr) on the plasma membrane. While it is recognized clinically that responsiveness of thyroid epithelial tumours to TSH varies with the histological type and grade of neoplasm, the level of TSHr expression in these different tumours has not been quantified hitherto. The aim of this study was to provide this information. Total RNA was extracted from 125 samples of formalin-fixed, paraffin-embedded thyroid tissue comprising 48 papillary (PTC), 29 follicular (FTC), eight anaplastic (ATC), and five medullary thyroid carcinomas (MTC), in addition to 35 samples of either follicular adenoma (FA) or normal thyroid tissue. Samples were reverse-transcribed and analysed using TaqMan polymerase chain reaction (PCR). TSHr expression was shown to be similar to normal in FA and inversely related to the grade of the majority of thyroid cancers other than MTC, in which, as expected, there was negligible expression. It is concluded that reduced expression of TSHr implies decreased responsiveness to TSH manipulation and is therefore a clinically important prognostic indicator in thyroid cancers.

Carcinoma↗

Expression of insulin-like growth factor receptors in primary human thyroid neoplasms.

The presence of IGF-I receptors was demonstrated in normal and neoplastic tissues of human thyroid. Binding of (125I)IGF-I to thyroid membranes was dependent on time and temperature of incubation, and maximal binding was achieved at 4 degree C and 18 h of incubation. (125I)IGI-I binding was dose-dependently displaced by unlabelled IGF-I; half-maximal inhibition occurred at concentrations of 10-20 milligrams. IGF-II and insulin had relative potencies of 5 and 1% compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with high affinity (Ka: 1.2-8.6 x 10(9) 1/mol) in normal thyroid tissues. Affinity cross-linking and autoradiography demonstrated the type IIGF receptors. Specific binding of (125I)IGF-1 in thyroid cancer tissues (9.69 +/- 2.07% per 200 micrograms protein; mean +/- SEM, N = 8) was significantly (p less than 0.05) higher than that in the surrounding normal tissues (3.03 +/- 0.35%, N = 8). In contrast there was no difference in the binding between adenoma tissues (4.19 +/- 0.53%, N = 5) and the adjacent normal tissues (2.94 +/- 0.24%, N = 5). The higher IGF-I binding in cancer tissues was due to an increase in the binding capacity without any change in the affinity. The presence of IGF-I receptors suggests a possible role of IGF-I and its receptors in the growth of thyroid cancer cells.

Adenoma↗

Feasibility of sentinel lymph node biopsy and lymphatic mapping in nodular thyroid neoplasms.

Although the prognostic significance of occult lymph node metastases in thyroid cancer remains controversial, identifying these patients may help direct therapy. The purpose of this study was to determine the feasibility and safety of sentinel lymph node biopsy (SLNBx) in thyroid nodular disease. Patients undergoing thyroid resection, with no evidence of clinical lymphadenopathy, were enrolled. The nodule was injected with isosulfan blue vital dye. Blue-stained lymphatic channels were traced within the central compartment to the SLN, which was excised. A total of 40 patients underwent SLNBx; lymphatics were seen in 31 patients, and SLNs were found in 26. In 11 patients the lymphatic vessels were traced through the central compartment into the lateral or mediastinal compartments, although a central SLN was retrieved in only 6. Of the 18 patients with benign neoplasms, 14 had benign SLNs, and no SLN was found in 4. A thyroid lymphoma patient had a true positive SLN. In the 12 patients with papillary thyroid cancer (PTC), 6 had true positive SLNs, and 2 had a true negative SLN. In one patient with metastatic PTC, the parathyroid stained blue. Another patient with PTC had lateral lymphatic channels, but no SLN was found. There were two false negatives, proven by a node dissection in one and lateral uptake on (131)I scanning in the other. There were no postoperative complications. SLNBx for thyroid disease is feasible and safe. Potential staining of the parathyroids makes their identification before injection mandatory. The variable lymphatic drainage patterns and the two false-negative nodes indicate that further investigation is required before the procedure can be recommended for patients with thyroid disease.

Adult↗

[Thyroid neoplasms and pregnancy].

Pregnancies and deliveries of ten patients are reported who underwent a complex treatment (surgery, 131J, thyroid hormone) for highly differentiated follicular and papillary thyroid carcinomas. Out of ten cases, in 3 cases two were pregnant and in two cases two delivered. Besides papillary and papillofollicular carcinomas, surgery revealed that six patients had regional lymph node metastases of N1 or N2. On the evidence of the deliveries, follow-up examinations after the operation, and complementary treatment of these two types of tumor, pregnancy is not contraindicated, since a progression of the primary disease, neonatal hypothyroidism, and factitious hyperthyroidism have not been found.

Carcinoma↗