EXPRESSION OF GROWTH-FACTORS AND GROWTH-FACTOR RECEPTORS IN NORMAL AND TUMOROUS HUMAN THYROID TISSUES

A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates with morphological alterations in proliferative lesions of thyroid, we examined the localization of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and their common receptor, EGF-receptor (EGF-R), insulin-like growth factor-1 (IGF-1), IGF-1-receptor (IGF-R) and IGF binding proteins (IGFBP)-1, -2, -3, and -4, nerve growth factor (NGF), and its receptor NGF-receptor (NGF-R), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF), in normal thyroid tissue and various thyroid tumors. We applied the streptavidin-biotin technique to formalin-fixed, paraffin-embedded tissues. We studied 8-16 different cases of each of the following: normal human thyroid, multi-nodular hyperplasia, follicular adenoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, and anaplastic carcinoma. EGF, TGF-alpha, and their receptor EGF-R were widely expressed in normal thyroid and in all the thyroid lesions examined. IGF-1 and IGFBP-1 were diffusely present in all different thyroid tissues as well. There was no difference in staining intensity or distribution that correlated with the pathological process. IGFBP-4 seemed to have a variable expression. IGFBP-2 and -3 were detected only in medullary carcinomas. NGF immunoreactivity was found in thyroid tissues and tumors of all types; interestingly, NGF-R staining was found in the vascular stroma and immunoreactivity correlated with the degree of vascularization, but no staining was seen in normal or lesional thyroid cells. TGF-beta expression was highly variable, whereas bFGF was not detected by this method in thyroid tissues. This study indicates that growth factors and growth factor receptors are expressed by thyroid follicular cells and C-cells. While they most likely play a role in cell regulation and proliferation in these tissues, their immunohistochemical profile does not correlate with the pathological condition

RADIATION-INDUCED TUMORS OF THE HEAD AND NECK

In order to study the induction of malignancy in normal tissues due to ionizing radiation, we reviewed the files of 2500 patients with a tumour of the head and neck treated at the Netherlands Cancer Institute (Antoni van Leeuwenhoek Ziekenhuis), Amsterdam, from 1977 to 1993. We then checked whether or not these patients had been previously irradiated. Patients with a thyroid carcinoma or skin cancer were excluded from the study, since it is generally known that previous irradiation is a risk factor in these tumours. Eighteen patients were found to have a malignancy within a previously irradiated area (0.70 per cent). The mean interval between radiation and diagnosis of the head and neck tumour was 36.5 years. There were five soft tissue sarcomas, nine squamous cell carcinomas and four salivary gland tumours. Fourteen patients were operated upon whereas four received palliative treatment only. The median survival of the total group was 3.5 years. Particularly, in young patients because of the better cancer therapy and prolonged survival one must be aware of the increased risk of radiation-induced tumours