Thirty-seven patients with medullary thyroid carcinoma were investigated to determine the status of adrenal medulla by computed tomography and 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy as well as measurements of urinary catecholamine excretion. Patients were followed up for 8 years in maximum. Fifteen patients belonged to multiple endocrine neoplasia type 2 including patients with incomplete phenotype. Computed tomography demonstrated adrenal tumors or enlargement in all 6 patients with urinary epinephrine (E) more than 30 micrograms/day, 4 of them were confirmed to have pheochromocytoma or adrenal medullary hyperplasia by surgery. In 2 patients with E less than 30 micrograms/day and epinephrine to norepinephrine (E/N) ratio more than 0.3 suggesting adrenal medullary hyperfunction, computed tomography revealed small adrenal tumors. Three of the remaining 7 patients with E less than 30 micrograms/day and E/N ratio less than 0.3 had equivocal enlargement of unilateral gland on computed tomography. 131I-MIBG scintigraphy demonstrated tracer uptake in adrenal glands with tumor more than 1cm in diameter. One of 2 adrenal glands with medullary hyperplasia showed a faint adrenal image on the scintiscan, but the other showed no tracer uptake. Pheochromocytoma became manifest in 4 patients during the follow-up period, 4, 13, 14 and 34 years after thyroid surgery. None of 22 patients with sporadic medullary thyroid carcinoma showed adrenal abnormalities on the examinations mentioned above.

Adenomatosis coli is recently regarded as a systemic disease with a predisposition to multiple tumor formation. We report siblings of familial adenomatosis coli with gastric cancers. Case 1 was a 58 year-old elder brother. His diagnosis was familial adenomatosis coli accompanied with colon cancer and simultaneous early gastric cancer. Total colectomy and partial gastrectomy were carried out on Mar. 13, 1984 at our hospital. Numerous polyps over the whole colon and an ulcerative tumor in the hepatic flexure were found in the resected colon. Histologically tubular adenocarcinoma were demonstrated in the ulcerative tumor, and all other polyps were adenomas. In the resected gastric specimen, there were two shallow, depressed lesions on the each anterior and posterior wall of the antrum. Histologically both of them were adenocarcinoma confined within the mucosa. Postoperative course was satisfactory and he is quite healthy 2 and a half years after surgery. Case 2 was a 56 year-old younger brother. He received a partial gastrectomy for advanced gastric cancer at another hospital on May 20, 1982. In one and a half year from the surgery, a large lung tumor (probably metastasis of the gastric cancer) was found and he received chemotherapy. He also received radiation therapy in June, 1984 and during this admission barium enema study was performed. It revealed numerous polyps over the whole colon. No cancerous lesions were found. He died of lung tumor on Dec. 8, 1985. The similar siblings were first reported by Kokaji et al. in 1984, and our cases seem to be the second ones.

Regulatory or structural alterations of c-onc genes including amplification, rearrangement and point mutation was implicated in the causation of various malignant tumors. However, such changes of molecular levels have not been reported so far in choriocarcinoma cells. In the present study, thus, 5 choriocarcinoma cell lines were analyzed by hybridization using 16 oncogene probes. By Southern blot hybridization of DNA extracted from these cells, 8 fold amplification of c-myc gene and rearrangement of c-fms gene were shown in ENAMI cells, although the role of these alterations remained unknown. Northern blot hybridization performed simultaneously demonstrated multiple expression of c-onc genes. 4 choriocarcinoma cell lines (HCCM, CHl, CCl, ENAMI) expressed at least 11 c-onc genes (H-ras, K-ras, N-ras, c-myc, N-myc, fos, fms, src, yes, erb B and raf); though the degree of expression of H-ras, C-myc, erb B and fms in these cells was either similar or enhanced as compared with normal fibroblast, the expression of two c-onc genes (N-myc and fos) was extremely enhanced. However, expression of K-ras and myb was either low or not detected. The multiple expression of c-onc genes seems to reflect partly on growth advantages of trophoblast. Transfection assay using NIH3T3 cells failed to form any transformed foci. Since choriocarcinoma cells which derived from the transformation of trophoblast of complete mole possess the genetic characteristics identical to the one of cells of complete mole, chromosomal instability was assumed to play a major role for multiple oncogene expression in choriocarcinoma cells.