Differentiated thyroid cancer, like breast cancer, prostatic cancer, and endometrial cancer of the uterus, is well known to be hormone sensitive. Experimental investigations have demonstrated that differentiated thyroid cancer cells have TSH (thyroid-stimulating hormone) receptor on the plasma membrane and that the growth regulation of differentiated thyroid cancer depends upon TSH. Therefore, suppression of TSH with thyroid hormone is rational for the treatment of recurrent thyroid cancer. Recurrent differentiated thyroid cancers reportedly cause regression in response to thyroid hormone administration, but the outcome of adjuvant therapy with thyroid hormone after operation for differentiated thyroid carcinoma is controversial. It is very difficult to analyze the difference in survival rate between the postoperative patient with and without thyroid hormone, because of the excellent postoperative survival rate of differentiated thyroid cancer patients. Further clinical studies and laboratory investigations about TSH suppression in adjuvant therapy for differentiated thyroid cancer are necessary to elucidate the impact of thyroid hormone on survival after operation.
We established a subclone, SHOK, from the GHE-L cell line, an immortal line derived from a primary culture of Syrian hamster embryo cells, as a recipient cell line useful for the detection of oncogenes by transfection. SHOK cells were almost as susceptible as NIH 3T3 cells to focus formation by many oncogenes, including v-raf, v-Ha-ras, v-Ki-ras, or activated c-Ha-ras. The susceptibility of SHOK to focus formation was higher than that of NIH 3T3 for v-mos but was lower for v-fps, v-fgr, v-src, v-sis, and v-abl. When DNAs extracted from 27 human and murine tumors were tested for focus formation, 5 DNAs were positive in NIH 3T3 cells, whereas 9 were positive in SHOK cells at the primary transfection. Using SHOK cells as recipients of tumor cellular DNA, we isolated another oncogene and a c-Ki-ras2 gene mutated at codon 146 that were difficult to detect in NIH 3T3 cells. SHOK cells have a low rate of spontaneous transformation, produce easily distinguishable foci, and maintain a stable karyotype in transformed cells. In addition to being useful for the screening of human tumor DNAs, SHOK cells will be useful for the isolation of oncogenes from murine tumors because of their hamster origin.
A Japanese family of 87 members in five generations with multiple endocrine neoplasia type 2A (MEN 2A) is described regarding the utility of screening tests for early detection of medullary thyroid carcinoma and the potential for DNA diagnosis of MEN 2A gene carriers. The screening programs for family members in this series include measurements of plasma calcitonin concentrations after intravenous injection of pentagastrin (0.5 micrograms/kg/5 sec) and 24-hour urinary excretion of catecholamines. While 18 MEN 2A patients had been previously diagnosed, these screening programs revealed five additional patients with MEN 2A (aged 16, 19, 35, 37, and 57). Prediction of MEN 2A gene carriers by DNA analysis has been attempted but is not yet possible in this family.
In 67 patients with medullary thyroid carcinoma, serum calcitonin levels were measured before (S1) and after (S2) surgical therapy. Doubling time of serum calcitonin levels (T2) was calculated in each patient with elevated calcitonin levels after surgery. Residual tumor weight (W2) was estimated as W1S2/S1-S2) where W1 was resected tumor weight. Reduction index (alpha) is defined as S2/S1 = (1/2) alpha. alpha T2 indicates expected prolongation in survival (EPS) by surgical therapy. Expected duration of survival after surgery (EDS) is estimated as beta T2, where beta times of doubling of the residual tumor (W2) make 1000 g of tumor which would generally kill the host. Death within 3 years after surgery or recurrence within 5 years was best associated with short EPS followed by short T2 or small alpha. Postoperative calcitonin levels had a rather weak correlation with the prognosis, and preoperative calcitonin levels had almost no correlation with the prognosis during the present observation period. All 3 patients with EDS shorter than 3.9 years died within 2 years and 2 months after surgery. These parameters allow quantitative judgement of the surgical benefit and quantitative prediction of the prognosis in each individual patient.
