Dedifferentiation of a transplantable papillary thyroid carcinoma over a 15-year period

Abstract

Fischer 344 rats on a prolonged low-iodine diet developed thyroid nodules which were transplanted subcutaneously into 33 thyroidectomized rats. One graft took and gave a papillary carcinoma. Serially transplanted syngeneically at 3to 4-month intervals, it became autonomous in third generation hosts. With electron microscopy examination it was microfollicular in year 8 and anaplastic, with totally unpolarized epithelial cells, in year 15. Basement membrane present in year I was no longer visible in specimens of years 8 and 15. Tight and gap junctions still present in year 8 were absent in year 15, although a few desmosomes persisted. From years 8 to 15, free ribosomes and microfilaments became more frequent, whereas the number of mitochondria and the development of the Golgi complex declined. male rats were fed a low-iodine diet (modified Remington) for several months according to a method previously described by Axelrad and Leblond. ' The animals developed enlarged thyroids showing hyperpla~ia'-~ of follicular epithelium and eventually nodules. I-' Fragments of these thyroids were transplanted by Mandavia and Nadler6.' under the skin of 33 thyroidectomized rats of the same inbred strain. Only one graft took, but it was successfully transplanted in all second generation animals. These were either normal rats placed on a lowiodine diet for 4 weeks prior to transplantation, or rats thyroidectomized 48 hours prior to transplantation, both groups being kept on a low-iodine diet following inoculation.6 Tumors from nonthyroidectomized rats on the low-iodine diet were successfully transplanted into all third generation hosts whether the recipients From the

Furan-Induced Hepatic Cholangiocarcinomas in Fischer 344 Rats

“…The histologic appearance of the transplanted cholangiocarcinomas remained similar to that of the original tumors and did not become anaplastic or less differentiated over the 8 serial passages. Similar results have been noted with transplants of liver tumors in the rat (21 ) and mouse (14), epidermal squamous cell carcinomas in the rat (26) and with rat thyroid tumors (20). The latter investigators noted no change in the morphology of the transplanted tumors until as late as the 16th passage or more, well beyond the scope of this study.…”

Cell kinetics of a rat thyroid transplantable tumour

“…At the 9th transplantation generation, TTT showed an infiltrative growth into the surrounding tissues and a moderate cellular pleomorphism. De-differentiation in tumour morphology and changes in functional activity have been observed by others in a variety of thyroid transplantable tumours (Wollmann et al, 1953;Mandovia et al, 1967;Matovinovich et al, 1968;Orvoine et al, 1983). Although there were dramatic changes in tumour morphology, TTT preserved its response to the changes in the level of TSH in the circulation.…”

“…The radiobiological properties and clinical responses of patients with low-grade differentiated follicular carcinomas treated with radioactive iodine support the above speculations. Data have also been published for the variability in the time that the TSH response is lost in other thyroid transplantable tumours during serial transplantation (Wollmann, 1963 ;Matovinovic et al, 1968;Orvoine et al, 1983). This variability in response of tumour cells to increased TSH levels is most probably the result of biological heterogeneity amongst primary solid tumours, as well as in the cell selection processes that occur during tumour progression (Beierwaltes & Al-Saadi, 1968;Noble, 1977).…”

“…A limited number of thyroid transplantable tumours (TTT) have been described in laboratory animals (Wollmann et al, 1953;Sinha et al, 1965;Mandavia & Nadler, 1967;Matovinovich et al, 1968;Orvoine et al, 1983). In the course of serial transplantations these tumours were predominantly studied with respect to changes in their morphology and functional activity (Wollmann et al, 1953;Beierwaltes & Al-Saadi, 1968;Orvoine et al, 1983). Thus, it was found that during the first few generations the thyroid transplantable tumours grew in animals only when there was an increased TSH level in the circulation.…”

Histological changes in TSH‐dependent tumours of the thyroid gland during serial transplantation in Fischer 344 rats

“…No systematic observations have been reported, however, on the histological nature of the transplanted tumours. From this time and up to the present, there have been many independent studies of the induction and various properties of thyroid tumours in the Fischer rat and other strains (Al-Saadi & Beierwaltes 1967;Tsuda et al 1976;Oshima & Ward 1986) but very limited information is available on the histological nature of the tumours and their phenotypic variation upon continued transplantation (see Orvoine et al 1983). This study of the histology of the transplanted tumours has been carried out over a period of 20 years.…”