The clonal origin of thyroid nodules and adenomas.
The clonal origin of thyroid tumors in female mice heterozygous for a deficiency of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) was studied. Tumor phenotype was demonstrated by enzyme histochemistry. Because monophenotypia is not synonymous with monoclonality, a method to estimate the degree of mingling of the two cellular phenotypes in normal tissue was devised. Twenty-five point three percent of 624 randomly chosen pairs of adjacent follicular cells were of unlike phenotype, suggesting that if tumors were derived from 2 or more cells at least a quarter would express polyphenotypia. Four hundred fifty-three thyroid lesions induced in 20 GPDX (enzyme-deficient) mice, 20 C3H (normal) mice, and 48 heterozygous (C3HxGPDX) mice by radiation and long-term goitrogen treatment were studied. One hundred twenty-eight adenomas (sharply defined or encapsulated hypercellular lesions) were found in heterozygotes; 108 (84%) were monophenotypic, and 20 (16%) were largely monophenotypic with degenerate areas or included normal cells. None were clearly polyphenotypic. Seventy-five nodules (circumscribed but not encapsulated, largely normocellular lesion with prominent stroma) were found in heterozygotes; 25 (33%) only were monophenotypic. It is concluded that thyroid adenomas are monoclonal and nodules polyclonal. The variegated pattern of polyphenotypia in the nodules together with their prominent stromal component leads to the suggestion that there is a causative role for the stroma in their generation.
Thomas
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GA
Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
Williams
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Williams
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D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D002999:Clone Cells; D008040:Genetic Linkage; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000235:genetics; D006579:Heterozygote; D006651:Histocytochemistry; D006720:Homozygote; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D013959:Thyroid Diseases / Q000235:genetics / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014960:X Chromosome