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Russo et al., Catanzaro, Catania and Roma, Italy, report for the
first time a somatic mutation of the TSH-receptor gene occurring in a thyroid
carcinoma. So far, mutations in the TSH-receptor gene have been reported
in toxic adenoma only. Toxic nodules very rarely are malignant. The present
report concerned a 60 year old female patient with a follicular carcinoma,
presenting as a toxic nodule with severe hyperthyroidism. The mutation
was only present in the malignant nodule, but not in the surrounding tissue
and was therefore a somatic mutation.
Williams, Cambridge, UK, reported on the pathological and molecular biological findings in thyroid cancers, reported in children exposed to fallout from the Chernobyl nuclear accident. Between 1990 and 1994, 298 cases of thyroid carcinoma in children, aged under 15 at the time of operation, were diagnosed. The histological diagnosis was virtually in all cases papillary carcinomas, many showing local invasion and many were of an unusual solid/follicular subtype. With regard to the molecular biological findings no activation was found of ras oncogene, while activation of ret oncogene by intrachromosomal rearrangement was found in 26% of cases, which findings are compatible with the known high frequency of double stranded breaks that occur after exposure to radiation. In a further report the same group, in combination with thyroidologists from Kiev, Ukraine and Minsk, Belarus, analyses 101 cases of papillary carcinoma, of which 58 were from areas exposed to fallout from the Chernobyl accident and 43 from an unexposed area. They analyse three rearrangements of the ret protooncogene that were present in 35% of the whole group. It appeared that ret activationwas not different in tumors from exposed and unexposed areas and there were no significant differences between adults and children. (Comment: It has recently emerged that intrachromosomal rearrangement of the ret proto-oncogene is associated with papillary carcinoma, whereas point mutations, that activate ret proto-oncogene, are associated with medullary carcinoma, either sporadic or as a component of multiple endocrine neoplasia IIa and IIb.) Santoro et al., Naples, Italy, and New Haven, Connecticut, USA, report an analysis of 300 human tumors for ret activation and demonstrated that in about 35% of papillary carcinoma ret activation occurs. Ret activation was not present in poorly differentiated and undifferentiated carcinomas. In the papillary carcinomas, microcarcinomas showed an especially high frequency of ret rearrangement (59%). Mayr et al., Hannover, Düsseldorf, Regensburg, Halle-Wittenberg, Germany, assessed the relevance of ret activation by rearrangement in 101 papillary thyroid carcinoma tumor specimens. They found in 8% ret activation and their analysis revealed that positivity for ret activation did not lead to increased risk of metastatic spread. Romei et al., Pisa, Italy, studied ret proto-oncogene activation by mutations in sporadic medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and primary parathyroid adenomas (PTA). They studied 25 tumor specimens MTC, 6 PTA and 15 PHEO. Ret mutations were analyzed in exon 1, 10, 11, 15, and 16. In 25 MTC patients, 1 patient had a germline mutation (thus appeared to suffer from a hereditary form), but in the other 24 MTC patients somatic mutations were found in 10 cases (41.6%). In 2 out of 15 PHEO patients a somatic mutation was found, but no mutation was present in 6 PTA patients. It is concluded that somatic ret mutations, but also sometimes deletions (1 patient) are frequently found in sporadic MTC, and further analysis showed that these patients are at high risk of tumor recurrence and metastases. Ret mutations are rarely found in sporadic PHEO and not in PTA. Husmark et al., Göteborg, Sweden, studied expression of E-cadherin (E-CAD) and of catenins (CATs) in one Hürthle cell adenoma, one Hürthle cell carcinoma, and one poorly differentiated/anaplastic thyroid carcinoma with metastatic spread. E-CADs are transmembrane adhesion molecules that play a role in formation of cell-adherence junctions and catenins are intracellular proteins that link E-CAD to the cytoskeleton and thus play also a role in cell to cell linking. It was already reported that thyroid carcinomas often show a reduced expression of E-CAD. Less is known about the catenins (alpha-, beta-, and gamma-catenins). In this study it was found that E-CAD expression was reduced to 10% in both Hürthle cell tumors and expression of catenins was unchanged. However, in the poorly differentiated/anaplastic thyroid carcinoma E-CAD expression was reduced, but also that of alpha-CAT and gamma-CAT. This preliminary study suggests that a highly malignant phenotype may be associated with specific alterations, not only of E-CAD, but also of catenins. (Comment: This is indeed a prelimi-nary study, and it should be extended to more cases. If the results with regard to catenins are confirmed in these further studies, determination of its expression may be used to determine the prognosis of the patient.) Dahlman et al., Uppsala, Sweden, studied the expression of integrins in cryosections of 58 normal and pathological thyroid specimens and of 3 lymphnode metastases from papillary carcinoma. Integrins (several alpha- and beta-forms) specifically play a role in interactions of cells with their extracellular matrix. Also E-CAD expression was studied. It was found that there was a gain of integrin expression a2 and a6, and a loss of E-CAD expression in anaplastic carcinoma, but not in follicular or papillary carcinoma. Smit et al., Leiden, The Netherlands, studied the function of b1 integrin in in vitro adhesion of 2 metastatic follicular thyroid carcinoma cell lines in culture. They found that both cell lines attached rapidly to calcified vertebrae and expressed b1 integrin. However, addition of antibody against b1 integrin prevented adhesion almost completely, indicating that b1 integrin may play a role in the metastatic tendency of these tumor cell lines. Belfiore et al., Catania, Italy, studied expression of the hepatocyte growth factor receptor (HGF-R) encoded by the proto-oncogene C-Met in 120 papillary carcinomas. They found that absent or low expression of HGF-R was associated with vascular invasion, which was present in 18.0% in HGF-R negative patients versus 4.3% in HGF-R positive patients. Its absence or low expression was also related to distant metastases (28.0% versus 2.9% respectively). (Comment: This observation also points to the possibility of determining the prognosis of a patient with papillary carcinoma by measuring HGF-R expression in tumor specimens.) Antonelli et al., Pisa, Italy, studied the epidemiology of thyroid carcinoma in children from the Gomel region in Belarus after the nuclear accident of Chernobyl in April 1986. Before the accident between 1981 and 1985 only 1 case of childhood thyroid cancer was reported from that area (rate = 0.5: annual average per one million children under 15 years). After the Chernobyl accident between 1986 and 1990, 21 cases (rate = 10.5) and between 1951 and 1955 another 143 cases (rate = 97) were detected, while in the first 7 months of 1995, 33 more cases were observed. Sixty-four children were studied. The female to male ratio was 1.4 : 1. The mean age at diagnosis was 9.5 ± 2.8 years and at the time of the accident 3.8 ± 2.4. The mean period of latency between the accident and the diagnosis was 5.6 ± 1.5 years. Over 90% of patients were less than 6 years of age at the time of the accident, and 3 were still in utero. There was no correlation between the age of the patients and the aggressiveness of the tumor. Pacini et al., Pisa, Italy, and Villejuif, France, reported on the epidemiology of thyroid carcinoma after the Chernobyl fallout from the whole area of Belarus, comprising 427 patients: 334 children (< 15 years) and 93 adolescents (15-21 years), and compared the results with 346 unexposed children and adolescents: 219 from Pisa and Rome, Italy and 127 from Villejuif, France. In Belarus children the mean age at the time of the accident was 3.3 ± 2.4 years and at diagnosis 10.0 ± 2.3 years in the adolescents 9.9 ± 2.7 years and 16.1 ± 1.1 years respectively. Time between exposure and diagnosis was similar in the two age groups. The overall female to male ratio was significantly higher in Italy and France (2.5 : 1) than in Belarus (1.6 : 1). In Belarus 94.6% tumors were papillary thyroid carcinoma (PTC), 4.7% follicular thyroid carcinoma (FTC) and 0.5% were medullary carcinoma (MTC). In the Italy-France series these figures were 82.0% PTC, 15.6% FTC, and 2.3% were unclassified. Extrathyroidal extension and lymphnode metastases were significantly more frequent in Belarus. In Belarus children the mean age at exposure was inversely related to aggressiveness of tumor at presentation. No such correlation was found in the children from Italy and France. Thyroperoxidase (TPO) antibodies were significantly more found in Belarus. Goslings et al., Leiden, The Netherlands, reported embolization of spinal metastases from follicular thyroid carcinoma in combination with 131I therapy in 6 patients. Embolization was effected by injection of Ivalon®. In 2 patients symptoms of paralysis disappeared completely and in 3 patients decreased substantially. In 1 patient no effect was seen. Cascone et al., Naples, Italy, studied the effect of octreotide injection (150 µg daily for 6 months and subsequently 300 µg daily for the next 6 months) in combination with recombinant interferon alpha 2b (3 times a week 5.000.000 IU intramuscularly for 12 months) in 8 patients with advanced medullary carcinoma. After 3 weeks, 2 patients were taken off the study because of aggravation of pre-existing diarrhoea and servere toxicity of interferon. In the other patients a maximal decrease in serum calcitonin was observed ranging between 88 and 34% of basal value and between 32 and 47% of basal value of CEA levels. Symptoms of diarrhoea and flushing disappeared in 4 and 1 patient respectively. (Comment: Although tumor markers decreased, no information was reported on any possible change of tumor mass. Symptomatic improvement, however, was present in several patients.) |
