Mapping of a gene predisposing to familial thyroid tumors with cell oxyphilia to chromosome 19 and exclusion of JUN B as a candidate gene.

BACKGROUND: Familial nonmedullary thyroid carcinoma (FNMTC) is a clinical entity characterized by a more aggressive phenotype than the sporadic counterpart. The transmission of susceptibility of FNMTC is compatible with autosomal dominant inheritance. We report the identification of a new entity of FNMTC and the mapping of the responsible gene named TCO (for thyroid tumor with cell oxyphilia). METHODS: In one family, multinodular goiters were diagnosed in six individuals and papillary thyroid carcinoma was diagnosed in three. Eight patients were operated on. Blood samples were collected from the nine affected patients and from eight unaffected relatives. The gene was mapped by linkage analysis with a whole-genome panel of microsatellite markers. RESULTS: The neoplastic cells from all lesions showed characteristic faint to marked cytoplasmic oxyphilia. We found a logarithm of odd ratio (LOD) score of 2.41 at theta = 0 for marker D19S586. Additional markers were typed in the region and were found to be in linkage, with LOD scores peaking at markers D19S916 (Zmax = 3.01 at theta = 0) and D19S413 (Zmax = 2.95 at theta = 0). All these markers have been physically mapped to 19p13.2. CONCLUSIONS: TCO was mapped to chromosome 19p13.2. Interestingly, both the benign and malignant thyroid tumors in this family exhibit some degree of oxyphilia, which has not been described until now in the familial forms of NMTC.

Adrenocortical carcinoma. A retrospective study of a rare tumor with a poor prognosis.

A retrospective study was performed on 54 patients diagnosed as having adrenocortical carcinoma during 1974-1983. The initial symptoms were often diffuse: abdominal pain, weight loss, or fever, and more than 60% of the patients showed no evidence of overproduction of hormone. The median tumor diameter was 13 cm and almost half of the tumors had metastasized at diagnosis. A radical tumor resection could be performed in less than 50% of the patients, and at histopathological re-examination some tumors were not conclusively verified as malignant. Capsular invasion, nuclear pleomorphism and mitoses were found more commonly in patients who succumbed to the disease. Seven of 29 patients treated with chemotherapy showed an objective response and two of them are still alive and free of disease. The overall 5-year-survival rate was 19%, compared with 45% for patients with radically resected tumors. Patients with no biochemical signs of overproduction of adrenocortical hormone appeared to have a better prognosis than those with hormone excess. Together with increased use of ultrasound and computed tomography, a urinary steroid profile might hopefully contribute to earlier discovery of these often clinically silent tumors. However, it remains to be determined whether these diagnostic improvements, together with more aggressive surgery and adrenolytic chemotherapy, can improve the poor prognosis.

Comparison of tumour markers in malignant mesothelioma and pulmonary adenocarcinoma.

Immunohistological methods were used to investigate the presence of carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin in formalin fixed tissue from 29 malignant mesotheliomas and 27 pulmonary adenocarcinomas. Malignant mesotheliomas were negative for tumour markers except for the beta subunit of human chorionic gonadotrophin and keratin, one and 13 cases respectively being positive for these. Pulmonary adenocarcinomas, however, were frequently positive for tumour markers--namely, carcinoembryonic antigen, beta 1 pregnancy specific glycoprotein, beta subunit of human chorionic gonadotrophin, human placental lactogen, calcitonin, and keratin. The presence of carcinoembryonic antigen and beta 1 pregnancy specific glycoprotein within an intrathoracic tumour is strong evidence against its being of mesothelial origin.